Egyptian Journal of Medical Human Genetics https://www.ajol.info/index.php/ejhg <p>The EJMHG is a peer reviewed journal that publishes articles in English reporting original investigations in the field of human and&nbsp;medical Genetics.</p> <p>The scope of the journal includes genetic basis of human disease such as clinical genetics and dysmorphology, cytogenetics, pharmacogenetics,&nbsp;cancer genetics, behavioral genetics, community genetics, screening of monogenic and polygenic disorders, fetal pathology,&nbsp;prenatal and pre-implantation genetic diagnosis and genetic counseling as well as advances in prevention and treatment of genetic&nbsp;disorders.</p> <p>The scope of the journal also includes biochemical genetics with an emphasis on biological studies of enzymes and other protein&nbsp;deficiencies and immunogenetics. In addition, the journal highlights fundamental investigations of the pathogenesis of inherited&nbsp;disorders and practical advances in the molecular diagnosis of human disease. Clinical application of genomics and next generation&nbsp;sequencing technologies are considered valuable contributions.</p> <p>The journal is published by the Egyptian Society of Human Genetics, Medical Genetics Center, Ain Shams University. It will consider&nbsp;reviews, review articles, original articles, case reports, announcements, editorials, editorial comments, correspondence, issue&nbsp;highlights, surveys and product reviews.</p> <p>© 2017 Ain Shams University. Production and hosting by Elsevier B.V. All rights reserved.</p> <p><strong>Notice</strong></p> <p>No responsibility is assumed by Egyptian Society of Human Genetics or Elsevier for any injury and/or damage to persons,&nbsp;property as a matter of products liability, negligence, or otherwise, or from any use or operation of any methods, products,&nbsp;instructions, or ideas contained in the material herein. Because of rapid advances in the medical sciences, in particular, independent&nbsp;verification of diagnoses and drug dosages should be made.</p> <p>Although all advertising material is expected to conform to ethical (medical) standards, inclusion in this publication does not&nbsp;constitute a guarantee or endorsement of the quality or value of such product or of the claims made of it by its manufacturer.</p> <p>Covered in the abstract and citation database Scopus®. Full text available on ScienceDirect®.&nbsp;</p> <p>Abstracts and journal information can be found at <a title="http://www.ejmhg.eg.net" href="http://www.ejmhg.eg.net" target="_blank" rel="noopener">http://www.ejmhg.eg.net</a></p> en-US Copyright is owned by the journal shawkyrabah@yahoo.com (Rabah M. Shawky) smnnrkm@yahoo.com (Dr. Nermine Salah El Dine) Mon, 14 Jan 2019 15:27:38 +0000 OJS 3.1.2.4 http://blogs.law.harvard.edu/tech/rss 60 MTHFR C677T polymorphism and risk of esophageal cancer: An updated meta-analysis https://www.ajol.info/index.php/ejhg/article/view/181774 <p><strong>Background:</strong> Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate/homocysteine metabolism. A polymorphism C677T has been reported to be linked with risk of several diseases/ disorders like birth defects, metabolic and psychiatric disorders and different cancers. The association between esophageal cancer and MTHFR gene C677T polymorphism has been investigated in several case-control studies, which rendered contradictory results.</p><p><strong>Aim:</strong> To shed light on association between MTHFR C677T polymorphism and risk of esophageal cancer, a meta-analysis of published case control association studies was conducted.</p><p><strong>Methods:</strong> Four electronic databases: PubMed, Google Scholars, Elsevier and Springer Link were searched up to August 2016. All statistical analyses were performed using MetaAnalyst and Mix (version 1.7). Odds ratios (ORs) with their 95% confidence intervals (95% CIs) were calculated. Total twenty-nine studies with 6520 cases and 9192 controls were included in the present meta-analysis.</p><p><strong>Results:</strong> The results of meta-analysis suggested that there were significant association between C677T polymorphism and esophageal cancer risk using overall comparisons in five genetic models (T vs. C: OR = 1.20, 95% CI = 1.1–1.27, p = &lt;0.0001; TT + CT vs. CC: OR = 1.37, 95% CI = 1.14–1.62, p = 0.0004; TT vs. CC: OR = 1.43, 95% CI = 1.1–1.84, p = 0.005; CT vs. CC OR = 1.35, 95% CI = 1.15–1.58, p = 0.0002; TT vs. CT + CC: OR = 1.19, 95% CI = 0.99–1.42, p = 0.05). Publication bias was absent. Subgroup analysis based on ethnicity and source of controls were also performed.</p><p><strong>Conclusion:</strong> In conclusion, results of present meta-analysis showed significant association between MTHFR C677T polymorphism and esophageal cancer.</p><p><strong>Keywords:</strong> Esophagial cancer, MTHFR, C677T, Meta-analysis, Homosycteine</p> Pradeep Kumar, Vandana Rai Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181774 Mon, 14 Jan 2019 00:00:00 +0000 Pathophysiology of bleeding diathesis in haemophilia-A: A sequential and critical appraisal of non-FVIII related haemostatic dysfunctions and their therapeutic implications https://www.ajol.info/index.php/ejhg/article/view/181777 <p>Haemophilia-A is characterized by deficiency of FVIII, but the bleeding diathesis is not a mere reflection low FVIII activity. The pathophysiology of haemophilic bleeding diathesis is a complex interplay between defective procoagulant function and up-regulated fibrinolysis. Moreover, haemophilic bleeding diathesis is frequently compounded by treatment-related and infective complications such as FVIII inhibitors, hepatitis, HIV infection, non-steroidal anti-inflammatory drugs (NSAID) induced gastritis, and infective mucosal injuries such as H pylori gastritis and intestinal and urinary helminthiasis. Hence, pathophysiology of haemophilic bleeding is multi-factorial, encompassing both FVIII and non-FVIII haemostatic defects. Currently available literature on pathophysiologic roles of non-FVIII haemostatic defects in haemophilia is fragmented. This articles is aimed at providing a composite and comprehensive review of the roles of non-FVIII haemostatic defects and their therapeutic implications in haemophilic bleeding diathesis, which will enable a holistic approach towards clinical management of the bleeding diathesis. This is necessary because FVIII therapy alone maybe insufficient in managing complicated haemophilic bleeding unless compounding non-FVIII-related haemostatic dysfunctions and comorbidities are identified, targeted and treated. This will necessitate appropriate use of non-FVIII therapeutic modalities, which may include anti-fibrinolytic agents, FVIII by-passing agents, immune modulation, and anti-microbial agents. Lots of work has been done in the areas of non-FVIII agents and FVIII by-pass therapy in the management of haemophilia, but more research is needed to validate many of these targeted therapeutic techniques. Meanwhile, healthcare personnel must consider the roles of both FVIII and non-FVIII haemostatic defects when evaluating haemophilic bleeding diathesis for the purpose of choosing appropriate and optimal treatment options.</p><p><strong>Keywords:</strong> Haemophilia, Bleeding diathesis, Pathophysiology, Targeted therapy, Non-FVIII therapy, FVIII by-pass</p> Umma A. Ibrahim, Sagir G. Ahmed Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181777 Mon, 14 Jan 2019 00:00:00 +0000 <i>Helicobacter pylori</i> Western <i>cagA</i> genotype in Egyptian patients with upper gastrointestinal disease https://www.ajol.info/index.php/ejhg/article/view/181778 <p><strong>Background:</strong> Infection with <em>Helicobacter pylori</em> (<em>H. pylori</em>) causes persistent gastritis that may progress to fatal gastric cancer. The cytotoxin-associated gene A protein (CagA), encoded by the <em>cytotoxin-associated gene A</em> (<em>cagA</em>) is the main virulence factor associated with more severe clinical outcomes. It is further divided into Western-type CagA and East Asian-type CagA. The East Asian-type CagA induces more cytoskeleton changes and is more likely to be associated with gastric cancer.</p><p><strong>Aim of the study:</strong> In the current study we aimed to identify the most prevalent<em> H. pylori cagA</em> genotype among Egyptian patients suffering from dyspepsia and to examine its possible correlation with the associated clinical condition.</p><p><strong>Patients and methods:</strong> Four biopsies were obtained from the antrum and angularis from each of 113 adult patients, who underwent upper endoscopy at the Endoscopy Unit, Theodor Bilharz Research Institute (TBRI) Hospital for the analysis of <em>H. pylori</em> by rapid urease test and detection of 16S rRNA. Nested PCR assay was used to determine cagA genotype.</p><p><strong>Results:</strong> Sixty (53.1%) dyspeptic patients were found infected with <em>H. pylori</em>. Although Egypt has a high prevalence of <em>H. pylori i</em>nfection, low prevalence of <em>cagA</em> was detected (26.5%). Western type cagA is the predominant type (62.5%) while East Asian type was not detected and others (37.5%) remain uncharacterized. Western-genotype<em> cagA</em> genotype was found in 80% of patients with peptic ulcer disease and 40% of patients with gastritis.</p><p><strong>Conclusion:</strong> Absence of the more virulent East Asian<em> cagA</em> genotype, which is the strongest risk factor for gastric carcinogenesis, may explain the very low gastric cancer rate among Egyptian population compared to other parts of the world. This finding demands further molecular studies using whole genome sequencing and more samples to determine the exact uncharacterized cagA genotype to identify the actual risk in developing gastroduodenal diseases in Egypt.</p><p><strong>Keywords:</strong> <em>Helicobacter pylori</em>, Endoscopic findings, Western type <em>cagA</em>, East-Asian <em>cagA</em>, Peptic ulcer, Gastritis</p> Manal Diab, Mohamed Shemis, Doaa Gamal, Ahmed El-Shenawy, Maged El-Ghannam, Effat El-Sherbini, Mohamed Saber Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181778 Mon, 14 Jan 2019 00:00:00 +0000 Fuzzy system model for gene expression https://www.ajol.info/index.php/ejhg/article/view/181781 <p><strong>Background:</strong> The theoretical information of a gene is contained in cell’s genetic materials, namely, DNA, mRNA and proteins. In the synthesis of functional gene products, this information can be expressed in mathematical way.</p><p><strong>Aim:</strong> In this paper, a fuzzy approach is used to analyse of the behaviour of a gene expression in a cell. The main aim of the present study is to unravel the complexity of gene expression and develop the mathematical model which can be used for better insight of functional gene products.</p><p><strong>Subjects and methods:</strong> The model for gene expression is obtained in terms of the system of fuzzy differential equations assuming that the transcription and translation processes are taking place in the cell. The Michaelis–Menten’s mechanism is incorporated in the model.</p><p><strong>Results:</strong> The analytic solution for crisp case as well as for fuzzy case is carried out. The sensitivity analysis is also performed and it is observed that the model is highly stable.</p><p><strong>Conclusion:</strong> The model for gene expression is obtained in terms of system of differential equations involving fuzzy initial values using geometric approach. The numerical results have been obtained for TJK16 strain of E.coli. The semi temporal concentrations profile of DNA, mRNA and protein are obtained and sensitivity analysis has been performed to study the variation in concentrations of DNA, mRNA and protein with respect to variation in transcription and translation rates.</p><p><strong>Keyword:</strong> Fuzzy Linear Differential equation model, DNA, mRNA, Protein, TJK16</p> Amit Sharma, Neeru Adlakha Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181781 Mon, 14 Jan 2019 00:00:00 +0000 <i>Angiotensin-converting enzyme (ACE) I/D</i> and <i>bradykinin B2 receptor T/C genes</i> polymorphism in patients with ACE inhibitors-related cough https://www.ajol.info/index.php/ejhg/article/view/181784 <p><strong>Background:</strong> Angiotensin-converting enzyme (ACE) inhibitors-related cough had been reported to contribute for discontinuation of ACE inhibitors therapy. The role of <em>ACE I/D</em> and <em>bradykinin B2 receptor T/C genes</em> in ACE inhibitors-related cough is still unclear.</p><p><strong>Objectives:</strong> To determine<em> ACE I/D</em> and<em> bradykinin B2 receptor T/C genes</em> polymorphisms in patients with ACE-inhibitors-related cough.</p><p><strong>Subjects and methods:</strong> An analytical study with cross-sectional design was conducted at Saiful Anwar General Hospital from June 2013 to September 2014. We used the polymerase chain reaction to genotype <em>ACE I/D</em> and <em>bradykinin B2 receptor T/C genes</em>. Data on both <em>ACE I/D</em> and <em>bradykinin B2 receptor T/C genes</em> polymorphisms in cough and non cough group of hypertensive patients treated with ACE inhibitors in our Hospital during the period were analyzed using multiple logistic regression. Moreover, a metaanalysis was performed to summarize findings from other regions.</p><p><strong>Results:</strong> A total of 18 patients with cough (21%) and 67 patients without cough (79%) of hypertensive patients treated with ACE inhibitors from our Hospital during the period were analyzed for this study. In our population, no correlation was observed between ACE inhibitors-related cough and both <em>ACE I/D</em> (p = 0.560) and<em> bradykinin B2 receptor T/C</em> (p = 0.475) genes polymorphism. However, our meta-analysis of five studies consisting of 267 patients with cough and 346 patients without cough revealed that higher risk of ACE inhibitors-related cough was 1.82-fold associated with T allele of <em>bradykinin B2 receptor T/C gene</em> polymorphism (p = 0.0310).</p><p><strong>Conclusions:</strong> While the evidence in our meta-analysis suggests strong role for <em>bradykinin gene</em> polymorphism in ACE inhibitors-related cough, however, in our population, we did not find any association.</p><p><strong>Keywords:</strong> ACE inhibitors-related cough,<em> ACE I/D</em> gene polymorphism, <em>Bradykinin B2 receptor T/C gene</em>, polymorphism, Hypertension</p> Mohammad Saifur Rohman, Jonny Karunia Fajar, Bagus Hery Kuncahyo, Lowry Yunita, Erdo Puncak Sidarta, Putu Nina Belinda Saka, Teuku Heriansyah, Nashi Widodo Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181784 Mon, 14 Jan 2019 00:00:00 +0000 Study of DNA methyl transferase 3A mutation in acute myeloid leukemic patients https://www.ajol.info/index.php/ejhg/article/view/181787 <p><strong>Background:</strong> Recent studies have shown that somatic mutations in DNA methyltransferase (<em>DNMT3A</em>) might affect the prognosis of AML.</p><p><strong>Objective:</strong> The aim of this work was to investigate the frequency and prognostic impact of the most frequent mutation of <em>DNMT3A</em>, R882H mutation in AML using simple and rapid molecular techniques.</p><p><strong>Patients and methods:</strong> We have used allele-specific blocker (ASB-PCR) and endonuclease restriction for the detection of <em>DNMT3A </em>R882H mutation in 56 adult patients with AML.</p><p><strong>Results:</strong> <em>DNMT3A</em> R882H mutation was detected in 7/56 (12.5%) of patients. R882H mutation positive patients were older compared to the wild-type AML (p = 0.08). No association was found with initial laboratory parameters including white blood cells (WBC), hemoglobin (HGB) and Bone marrow (BM) blasts (p &gt; 0.05). Thirty-two patients (57.1%) achieved complete remission (CR), 11/56 (19.6%) died before day 28 induction death (ID) and 13/56 (23.2%) had resistant disease (RD).<em> DNMT3A</em> R882H positive patients were not different regarding the response to induction chemotherapy (CR) compared to the negative group (wild-type) (p &gt; 0.05). Median follow-up period for all patients was 1.6 months, Overall survival (OS) was 65%, and the median was 9.89 months. OS of <em>DNMT3A</em> positive patients was not statistically significant compared to wild-type patients (p = 0.09). Disease free survival (DFS) was 54.6% for all patients, with no difference between wild and mutants (0.59) patients.</p><p><strong>Conclusion:</strong> <em>DNMT3A</em> R882H is a frequent mutation in adult de novo AML. The frequency of the mutation tends to increase with age. The two methods used in the study are easy to interpret and are recommended for rapid detection of the mutation required for risk stratification.</p><p><strong>Keywords:</strong> AML, <em>DNMT3A</em>, ASB-PCR, PCR-RFLP, Endonuclease restriction</p> Ghada M. Elsayed, Abd Elgawad A. Fahmi, Nevine F. Shafik, Reham A.A. Elshimy, Heba K. Abd Elhakeem, Sara A. Attea Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181787 Mon, 14 Jan 2019 00:00:00 +0000 Left ventricle myocardial performance in Down Syndrome children with clinically and anatomically normal hearts: Relationship to oxidative stress https://www.ajol.info/index.php/ejhg/article/view/181789 <p>Oxidative stress is implicated in many organs pathophysiologies in Down syndrome. Scarce data exist concerning left ventricular (LV) performance in DS children with normal hearts. Tissue Doppler derived myocardial performance index (TDI-Tei index) is a reliable method for ventricular performance evaluation. Myeloperoxidase (MPO) enzyme plays a crucial role in oxidants production and is a marker of cardiovascular risk.</p><p><strong>Aim:</strong> To evaluate LV myocardial performance in DS children with normal hearts using TDI-Tei index and correlate it with plasma MPO as a marker of oxidative stress.</p><p><strong>Patients and methods:</strong> This cross-sectional study included 120 DS children recruited from Children s Hospital, Ain Shams University. Out patients clinic and echocardiography unit (mean age, 8.35 ± 4.25 years) who were subjected to: history taking, clinical examination, laboratory investigations (Complete blood count, serum Alanine Transaminase, serum creatinine, Thyroid profile, 12 lead Electrocardiogram and conventional Doppler echocardiography). DS children with congenital or acquired heart diseases, dysrhythmias, anaemia, pulmonary hypertension, thyroid, renal disease, diabetes were excluded. The remaining 50 DS children with normal hearts (group I) were compared to 50 age. Sex matched healthy children as control (group II) Studied groups were subjected to: plasma MPO using ELISA technique and TDI LV-Tei index assessment using Vivid E9 Echocardiography machine (GE, Horton, Norway).</p><p><strong>Results:</strong> LV TDI-Tei was significantly increased in group I compared to group II (0.46 ± 0.02 vs 0.32 ± 0.08, p &lt; 0.001). Plasma MPO was increased in group I than group II (64.4831 ± 0.6 ng/ml vs 50.4 ± 30.2 nglml, p &lt; 0.001). A significant positive correlation was found between plasma MPO and LV TDI-Tei (r = 0.877, p = 0.001) in group I.</p><p><strong>Conclusion:</strong> Subclinical Left ventricle dysfunction evidenced by increased TDI Tei index was detected in DS children with normal hearts. This dysfunction correlated with plasma MPO level which mandates antioxidants treatment and tissue Doppler myocardial performance regular evaluation for early identification, monitoring and early intervention.</p><p><strong>Keywords:</strong> Left ventricle, Tissue doppler, Tei index, Oxidants, DS with normal hearts</p> Omneya Ibrahim Youssef, Soha Youssef Raouf Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181789 Mon, 14 Jan 2019 00:00:00 +0000 Impact of PAI-1 4G/5G and C > G polymorphisms in acute ST elevation myocardial infarction and stable angina patients: A single center Egyptian study https://www.ajol.info/index.php/ejhg/article/view/181791 <p><strong>Background:</strong> Many genetic factors, including polymorphisms in the genes regulating blood coagulation and fibrinolysis have been proposed as risk factors for coronary artery disease (CAD). PAI-1 is the chief inhibitor of tissue plasminogen activator and urokinase plasminogen activator. PAI-1 has a crucial role in regulation of fibrinolysis.</p><p><strong>Aim of the study:</strong> Is to investigate the association between Plasminogen activator inhibitor-1 (PAI-1) 4G/5G, PAI-1C/G polymorphisms and CAD. In addition, studying the relation of these polymorphisms to the level of active PAI-1 in Egyptian patients presenting to a single tertiary center in Cairo.</p><p><strong>Subjects and methods:</strong> One hundred and forty-four patients were included in this study: 42 STEMI (ST elevation myocardial infarction) patients, 63 stable angina patients, and 39 as a control group. Detection of PAI-1 4G/5G and C &gt; G polymorphisms was done using allele specific polymerase chain reaction and restriction fragment length polymorphism (RFLP) respectively. Plasma plasminogen activator inhibitor-1 activity was detected using enzyme linked immunosorbent assay (ELISA).</p><p><strong>Results:</strong> In the studied CAD patients, PAI-14G/5G polymorphism showed 31.7%, and 68.3% for 5G/5G, and (4G/5G + 4G/4G) respectively; however for the control group, 5G/5G, and (4G/5G + 4G/4G) were detected in 21.6%, and 78.4% respectively (p value 0.59). The genotypic frequencies for PAI-1C/G in CAD patients accounted for 27% (CC), 73% (CG + GG); while in the control group these frequencies were 35.3%, and 64.7% respectively (p value 1.43).</p><p><strong>Conclusion:</strong> No significant association between PAI-1 4G/5G and C &gt; G polymorphisms and the risk of coronary artery disease or the activity level of PAI-1 among the studied Egyptian population sample. However, STEMI patients showed significant presence of combined mutant allele of both genes more frequently.</p><p><strong>Keywords:</strong> Coronary artery disease, Plasminogen activator inhibitor, Genetic polymorphism, 4G/5G, C&gt;G</p> Hanan Al-Wakeel, Nadia Sewelam, Mohamed Khaled, Akram Abdelbary Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181791 Mon, 14 Jan 2019 00:00:00 +0000 Pathogenic predictions of non-synonymous variants and their impacts: A computational assessment of <i>ARHGEF6</i> gene https://www.ajol.info/index.php/ejhg/article/view/181793 <p><strong>Introduction:</strong> ARHGEF6, a key member and activator of RhoGTPases family that is involved in G-Protein Coupled receptor (GPCR) pathway and stimulate Rho dependent signals in the brain, and mutations in this gene can cause intellectual disability (ID) in Human. Therefore, we aimed to study the consequences of <em>ARHGEF6</em> non-synonymous mutations by using advanced computational methods.</p><p><strong>Methods:</strong> Classification of the genetic mutations in<em> ARHGEF6</em> gene was performed according to Ensembl Genome Database and data mining was done using ensemble tools. The functional and disease effect of missense mutations, and pathogenic characteristics of amino acid substitutions of<em> ARHGEF6</em> were analyzed using eleven diversified computational tools and servers.</p><p><strong>Results:</strong> Overall, 47 <em>ARHGEF6</em> non-synonymous (NS) variants were predicted to be deleterious by SIFT, Polyphen2 and PROVEAN scores. Above that, SNPs&amp;GO and PhD SNP were further graded 21 customarily pathogenic NS-variants. Protein stability analysis resulted in the significant change in terms of <span>△<span>△</span></span>G of most identified NS-variants, except K609I. Seven variants were analyzed to be located on most potential domain RhoGEF/DH, whereas the remaining 14 were distributed on CH, SH3, PH and BP domains. Furthermore, pathogenic effects of mutations on protein was presented with different parameters using MutPred2 and PROJECT HOPE. Additionally, STRING network data predicted GIT2 and PARVB as most interacted partners of ARHGEF6.</p><p><strong>Conclusion:</strong> These findings can be supportive of genotype-phenotype research as well as the development in pharmacogenetics studies. Finally, this study revealed a significance of computational methods to figure out highly pathogenic genomic variants linked with the structural and functional relationship of ARHGEF6 protein.</p><p><strong>Keywords:</strong> Computational methods, <em>ARHGEF6</em>, Intellectual disability, Missense mutation</p> Yashvant M. Khimsuriya, Jenabhai B. Chauhan Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181793 Mon, 14 Jan 2019 00:00:00 +0000 FLT3 receptor/CD135 expression by flow cytometry in acute myeloid leukemia: Relation to <i>FLT3</i> gene mutations and mRNA transcripts https://www.ajol.info/index.php/ejhg/article/view/181796 <p><strong>Background:</strong> Alterations of the <em>FLT3</em> gene are the most frequent molecular aberrations seen at diagnosis of acute myeloid leukemia (AML). Two main types of <em>FLT3</em> mutations have been the most commonly detected; internal tandem duplication (ITD) in the juxtamembrane domain and point mutation D835Y in the tyrosine kinase domain (TKD). Both classes of mutations result in constitutive activation of FLT3 receptor/CD135.</p><p><strong>Aim:</strong> To assess the frequency of <em>FLT3</em> gene mutations (ITD and TKD D835Y) and the flow cytometric expression of FLT3 receptor/CD135 among AML patients to define the role for<em> FLT3</em> receptor expression in predicting FLT3 gene mutational status and mRNA transcript level.</p><p><strong>Subjects and methods:</strong> Eighty AML patients at diagnosis and 20 control subjects were enrolled. FLT3 receptor/ CD135 expression, <em>FLT3</em> gene mutations, and <em>FLT3</em> transcript level were evaluated by flow cytometry, conventional polymerase chain reaction (PCR), and quantitative real-time reverse-transcription PCR, respectively. Fluorescence in situ hybridization was done to stratify patients into favorable, intermediate, and poor cytogenetic risk groups.</p><p><strong>Results: </strong><em>FLT3</em>-ITD was detected in 22.5% AML patients, while none had <em>FLT3</em>-TKD D835Y mutation. A cutoff value of &gt;17% was assigned to define FLT3 receptor/CD135<sup>+</sup> cases. FLT3 receptor/CD135 and<em> FLT3</em> transcripts were overexpressed in 100% AML patients; higher levels were found among AML-M5 subtype and poor cytogenetic group. AML patients harboring <em>FLT3</em>-ITD showed a trend for higher FLT3 receptor/CD135 expression and FLT3 transcript level than those with wild-type<em> FLT3</em>. FLT3 receptor/CD135 &gt;49% was predictive for<em> FLT3</em>-ITD. A positive correlation was found between FLT3 receptor/CD135 expression and FLT3 transcript level.</p><p><strong>Conclusion:</strong> Evaluation of FLT3 receptor/CD135 expression by flow cytometry at diagnosis of AML could constitute a predictor for the <em>FLT3</em>-ITD mutational status and FLT3 transcript level.</p><p><strong>Keywords:</strong> Acute myeloid leukemia, CD135, FLT3 receptor, <em>FLT3</em> mRNA, <em>FLT3</em>-ITD, <em>FLT3</em>-TKD</p> Mohamed Amin Mekawy, Deena Samir Eissa, Mohamed Tarif Hamza, Gehan Mostafa Hamed, Mariam Karam Youssef Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181796 Mon, 14 Jan 2019 00:00:00 +0000 Evaluation of health-related quality of life and muscular strength in children with beta thalassemia major https://www.ajol.info/index.php/ejhg/article/view/181798 <p><strong>Background:</strong> Thalassemia is an inherited blood disorder that requires repeated blood transfusions and chelation regimes. This may lead to restrictions in physical activities, social participation as well as decreased muscle strength.</p><p><strong>Aim:</strong> The aim of this study was to evaluate the health-related quality of life (HRQoL), muscular strength and pain in children with β-thalassemia major.</p><p><strong>Patients and method:</strong> One hundred and twenty children (60 with <span>β</span>-thalassemia major and 60 age-matched healthy) were participated in a cross-sectional study from both sexes (57 girls and 63 boys) with ages ranging from two to twelve years. HRQoL (physical, emotional, social and school functioning), muscular strength and pain were evaluated for all children by using the pediatric quality of life inventory<sup>TM</sup> (PedsQL<sup>TM</sup>) 4.0 generic core scale, hand-held dynamometer and visual analogue scale (VAS) respectively.</p><p><strong>Results:</strong> Children with β-thalassemia major showed a significant decrease in all domains of health-related quality of life and handgrip strength with a significant increase in VAS score (p <span>≤</span> 0.0001).</p><p><strong>Conclusions:</strong> The study concluded that thalassemia as a chronic disease has a negative impact on HRQoL and muscle strength of children in different age group.</p><p><strong>Keywords:</strong> Beta thalassemia, Quality of life, Handgrip strength, children</p> Dina K. Ismail, Mona H. El-Tagui, Zeinab A. Hussein, Mohamed A. Eid, Sobhy M. Aly Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181798 Mon, 14 Jan 2019 00:00:00 +0000 Study of congenital malformations in infants and children in Menoufia governorate, Egypt https://www.ajol.info/index.php/ejhg/article/view/181799 <p>Congenital anomalies is one of the main causes of physical disabilities, stillbirths and neonatal deaths. The exact etiology of most congenital anomalies is unidentified but genetic and environmental causes are accused.</p><p>We aimed to study congenital anomalies regarding frequency, clinical pattern and associated risk factors.</p><p>A cross-sectional study was conducted on 100 infants and children with congenital anomalies attended to our pediatric genetic clinic at Menoufia University Hospital from October 2016 to October 2017. Detailed history taking, clinical examination and investigations including cytogenetic study were done.</p><p>Out of 100 cases, 51% have isolated anomalies and 49% have multiple anomalies, 14.2% had chromosomal abnormalities, 44.8% were diagnosed as genetic syndromes, while we did not reach the final diagnosis in 40.8% of cases. According to the ICD-10 classification of congenital anomalies musculoskeletal system anomalies were the most common in 48% of cases, followed by anomalies of the eye, ear, face and neck in 44% of cases. Anomalies of nervous system, circulatory system, genital organs, urinary system, chromosomal abnormalities, cleft lip and cleft palate occur in 26%, 22%, 18%, 12%, 7% and 6% of cases respectively.</p><p>Gastrointestinal anomalies in only 4% of cases taking into account that one case may have more than one affected system. According to the guidelines for case classification for the National Birth Defects Prevention Study, 2003, 51% had major anomalies, 18% had minor anomalies while 31% had both. Some cases had undergone immediate intervention e.g. meningomyelocele, encephalocele, omphalocele and gastroschisis. While other cases required later intervention e.g. hypospadius, cleft palate and cleft lip. Male gender, consanguineous marriage and lack of maternal folic acid supplementations were found in 54%, 43% and 59% of cases respectively, constituted the main risk factors.</p><p><strong>Subjects and methods:</strong> proper physical examination, cytogenetic and molecular studies are important for the early intervention so prevention will be possible.</p><p><strong>Keywords:</strong> Anomalies, Chromosomal, Congenital, Dysmorphic, Syndrome, Diagnosis</p> Soheir S. AbouEl-Ella, Maha A. Tawfik, Wafaa Moustafa M. Abo El-Fotoh, Mai A. Elbadawi Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181799 Mon, 14 Jan 2019 00:00:00 +0000 <i>In silico</i> analysis of the functional non-synonymous single nucleotide polymorphisms in the human CYP27B1 gene https://www.ajol.info/index.php/ejhg/article/view/181800 <p><strong>Background:</strong> CYP27B1 gene codes for 25-hydroxyvitamin D<sub>3</sub> 1-a-hydroxylase, an enzyme that catalyses the activation of vitamin D to the 1-a, 25 dihydroxyvitamin D<sub>3</sub>. The activity of this enzyme is altered by non-synonymous single nucleotide polymorphisms (nsSNPs) located within its gene. Such alterations consequently affect the synthesis of the active form of the hormone, 1-a, 25 dihydroxyvitamin D<sub>3</sub>, resulting in vitamin D deficiency or insufficiency.</p><p><strong>Objective:</strong> We aimed to investigate the impact of nsSNPs in the CYP27B1 gene on the structure and/or function of 25-hydroxyvitamin D<sub>3</sub> 1-a-hydroxylase.</p><p><strong>Methods:</strong> The pathogenic nsSNPs in the human CYP27B1 obtained from National Centre for Biotechnology Information (NCBI) were analysed for their structural and functional consequence using mutation analysis algorithms like Consurf, I-Mutant, and MutPred. The effects of the mutation on tertiary structure of the human CYP27B1 protein was predicted using SWISS-MODEL while STRING was used to investigate its protein–protein interaction.</p><p><strong>Results:</strong> Out of 938 SNPs in the human CYP27B1 gene, 455 that are responsible for missense mutations in the protein were subjected to various prediction algorithms to identify the pathogenic variants. Out of 24 consensus pathogenic nsSNPs, our Consurf analysis showed that mutations at conserved positions T321, R389 and G125 will significantly alter the structure of human CYP27B1 protein. These mutations also alter the metal binding and result in intrinsic structural disorder. These consequently, alter the 3D structure of the protein and could impact its ability to interact with other proteins like Cytochrome P450, family 2, subfamily R, polypeptide 1; Cytochrome P450, family 24, subfamily A, polypeptide 1 and Vitamin D receptor, that are involved in vitamin D pathway, as revealed by STRING.</p><p><strong>Conclusion:</strong> These nsSNPs could contribute to vitamin D deficiency and its associated pathological conditions.</p><p><strong>Keywords:</strong> Polymorphisms, CYP27B1, Vitamin D, Mutation, Cancer, Diabetes</p> Solomon O. Rotimi, Olamide Peter, Oluwayomi Oguntade, Oluwakemi A. Rotimi Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181800 Mon, 14 Jan 2019 00:00:00 +0000 Renalase gene polymorphisms (rs2576178 and rs10887800) in Egyptian hypertensive end stage renal disease patients https://www.ajol.info/index.php/ejhg/article/view/181803 <p><strong>Background:</strong> The highly polymorphic gene encoding human renalase (RNLS) is a 311,000 bp gene located on chromosome 10.</p><p><strong>Aim:</strong> This study aimed at studying the possible association of the two RNLS gene polymorphisms rs2576178 and rs10887800 with chronic kidney disease in general or specifically with hypertensive nephropathy in Egyptian end stage renal disease (ESRD) patients on maintenance hemodialysis.</p><p><strong>Subjects and method:</strong> This case control study was conducted on two hundred and eighty one individuals, divided equally into two groups; an end stage renal disease patients on maintenance hemodialysis with/without hypertension and healthy matching individuals as a control group. Full clinical examination, Biochemical analysis and Molecular genetic testing were performed to detect single nucleotide polymorphism using restriction fraction length polymorphism (RFLP) for RNLS rs2576178 and rs1088780.</p><p><strong>Results:</strong> The results of this study demonstrated that the risk of developing ESRD was increased among carriers of AA genotype for the rs10887800 (3.05 times) p = 0.001, OR = 3.05, CI95% (1.558–5.971) and GG genotype for the rs2576178 p = 0.047, OR = 1.949, CI95% (1.028–3.694).</p><p><strong>Conclusion:</strong> Our study revealed that the risk of developing end stage renal diseases was increased among carriers of AA genotype for the rs10887800 polymorphism and GG genotype for the rs2576178 polymorphism.</p><p><strong>Keywords:</strong> End stage renal disease, Renalasegene polymorphism, Hemodialysis, Hypertenion</p> Noha S. Kandil, Rania Mohamed El Sharkawy, Lubna Mohamed Ibrahim Desouky, Lamia Said Kandil, I.M. Masoud, Noha Gaber Amin Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181803 Mon, 14 Jan 2019 00:00:00 +0000 Study of the role of IL-17F gene polymorphism in the development of immune thrombocytopenia among the Egyptian children https://www.ajol.info/index.php/ejhg/article/view/181804 <p><strong>Background:</strong> Interleukin 17F (IL-17F) is a pro-inflammatory cytokine that is recently proved to have a crucial role in the emergence of autoimmune diseases; it induces the expression of various cytokines, chemokines, and adhesion molecules. IL-17F polymorphism is subsequently related to enhanced IL-17F expression and activity; which may result in susceptibility to many autoimmune diseases including primary immune thrombocytopenia (PIT).</p><p><strong>Aim of the study:</strong> This case-control study aimed to investigate the possible association between IL and 17F gene single nucleotide polymorphism (SNP) at rs 7488A/G and PIT susceptibility in Egyptian pediatric patients.</p><p><strong>Subjects and methods:</strong> A total of 50 children with PIT with a mean age of 7 years, together with 50 age and sexmatched healthy controls were enrolled in the study for evaluation. Polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) was used for detection of IL-17F polymorphism at rs7488A/G.</p><p><strong>Results:</strong> Regarding the genotypes distribution, the frequencies of the AA, AG and GG genotypes were 96, 2, and 2% in PIT patients and 90, 10 and 0% in the control group respectively. The A and G allele frequencies were 97 and 3% in the patients’ group versus 95 and 5% in the control group. There was no significant difference in either genotypes or allelic distribution between PIT patients and the controls.</p><p><strong>Conclusion:</strong> Our study suggests that IL17F gene polymorphism at rs7488A/G may not contribute to the susceptibility in development of primary immune thrombocytopenia in the Egyptian children.</p><p><strong>Keywords:</strong> Interleukin 17F (IL-17F), Primary immune thrombocytopenia (PIT), Single nucleotide polymorphism (SNP), Polymerase chain reaction-restriction, fragment polymorphism (PCR-RFLP)</p> Shahira K.A. Botros, Ola M. Ibrahim, Alaa A. Gad Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181804 Mon, 14 Jan 2019 00:00:00 +0000 Metadherin mRNA expression in hepatocellular carcinoma https://www.ajol.info/index.php/ejhg/article/view/181806 <p><strong>Background:</strong> Metadherin (MTDH) has been known as an essential oncogene in carcinogenesis and tumor spread in several malignancies, via its effect on pathways of signal transduction.</p><p><strong>Objective:</strong> We aimed to evaluate the role of serum MTDH mRNA expression in the diagnosis of hepatocellular carcinoma (HCC) and to compare its expression levels with serum levels of Alpha-fetoprotein (AFP).</p><p><strong>Subjects &amp; methods:</strong> A total of 150 subjects (90 HCC patients &amp; 60 healthy volunteers) were enrolled in the current study. Serum MTDH mRNA relative expression was analyzed by Real Time PCR technique.</p><p><strong>Results:</strong> There was a significant statistical increase of serum MTDH mRNA expression in HCC group when compared to controls (P &lt; 0.05). MTDH mRNA expression was significantly associated with clinicopathological data, advanced tumor stage and poor histological differentiation in HCC patients (p &lt; 0.05). There was direct positive correlation between MTDH mRNA expression and serum AFP levels in HCC group (r = 0.445), P value = &lt;0.05. ROC curve was used to verify the accuracy of MTDH mRNA expression and compare it with accuracy of serum AFP in HCC diagnosis; MTDH mRNA expression had higher accuracy (92%), sensitivity (91%) and specificity (93%) than AFP.</p><p><strong>Conclusion:</strong> MTDH mRNA is up-regulated in serum of HCC patients; MTDH may be considered as noninvasive biomarker for HCC diagnosis and it could replace serum AFP in HCC diagnosis as it had higher accuracy.</p><p><strong>Keywords:</strong> Biomarker, Expression, Hepatocellular carcinoma, Metadherin, Real Time PCR</p> Nevein M. Al-sheikh, Sally M. El-Hefnway, Ahmed M. Abuamer, Ashraf G. Dala Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181806 Mon, 14 Jan 2019 00:00:00 +0000 The cephalofacial characterization in humans: The study using igbo tribe in Nigeria https://www.ajol.info/index.php/ejhg/article/view/181809 <p><strong>Background:</strong> Cranial and facial indices are among the most important craniofacial parameters most useful racial classification, categorization and forensic examination. In this, cranial and facial parameters serve as bio-anthropological tools for both biometric and crime scene purposes in the developed nation. Despite the rise in crime scenes and body mutilations in Nigeria, very little information is available on anthropometric variables using head and face of Igbo extractions.</p><p><strong>Aim:</strong> Aim of this study is to establish facial and head anthropometry in the bio-anthropological database for the South-Eastern Nigerians.</p><p><strong>Materials and methods:</strong> A total of 189 healthy individuals without cranial or facial deformities in Urban Secondary School, Abakaliki in Ebonyi State were recruited for the study.</p><p><strong>Results:</strong> The results of the study showed that male facial parameters had significantly higher dimensions than those of the female participants. The association between cranial and facial dimensions, sex and age using Pearson’s correlation analysis was done. Linear regression analysis was applied to determine<br />strength of relationship of the facial dimensions and age. The level of statistical significance was determined at P &lt; 0.05 with confidence interval at 95%.</p><p><strong>Conclusion:</strong> the study characterized anthropometrics of face and head of Igbos in the South-Eastern region of Nigeria. From this study, Igbo ethnic group fall under the platyrrhine type of nose. Igbo males and Igbo females are mesocephalic from this study. On the average from this work, the mean C.I. in the Igbo tribe belongs to mesocephalic or medium headed population.</p><p><strong>Keywords:</strong> Abakaliki, Cephalofacial, Igbos, Forensic, Parameters</p> Obaje Godwin Sunday, Uzomba Godwin Chinedu Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181809 Mon, 14 Jan 2019 00:00:00 +0000 A study on the association of TCF7L2 rs11196205 (C/G) and CAPN10 rs3792267 (G/A) polymorphisms with type 2 diabetes mellitus in the South Western of Iran https://www.ajol.info/index.php/ejhg/article/view/181810 <p><strong>Background:</strong> Type 2 diabetes mellitus is a multifactorial and heterogenic disease with a complex etiology. In recent decades the association of a large number of genes has been shown with T2DM. <em>CAPN10</em> gene was the first T2DM candidate gene identified through genome-wide screening and positional cloning, and among all identified genes until now, <em>TCF7L2</em> gene has shown most association with T2DM. The aim of this study was to investigate the association between <em>TCF7L2</em> rs11196205(C/G) and <em>CAPN10</em> rs3792267 (G/A) with T2DM in a subset of Iranian population from Khuzestan province. It should be noted that this is the first report of <em>TCF7L2</em> polymorphism rs11196205with T2DM in Iran.</p><p><strong>Subjects and methods:</strong> A case-control association study was performed using 150 T2DM patients and 150 controls. Genotyping for<em> TCF7L2</em> rs11196205 was done by Tetra-Primer ARMS-PCR and for <em>CAPN10</em> rs3792267 was done by PCR-RFLP Technique.</p><p><strong>Results:</strong> Statistical analyses were carried out using SPSS version 16. In examining TCF7L2 rs11196205 based on the genotype GG, results for CG genotype were, 95%CI = (0.5–1.7), OR = 0.92, P-value = 0.79 and for genotype CC were, 95%CI = (0.94–3.92), OR = 1.92, P-value = 0.07. in examining <em>CAPN10</em> rs3792267 based on the genotype AA, results for GG genotype were, 95%CI = (0.55–6.8), OR = 1.93, P-value = 0.31 and for genotype GA were, 95%CI = (0.43–5.64), OR = 1.55, P-value = 0.5. So, in both polymorphisms, none of the alleles or genotypes had significant statistical differences between case and control groups (P &gt; 0.05).</p><p><strong>Conclusion:</strong> Our results showed that TCF7L2 rs11196205 and <em>CAPN10</em> rs3792267 (SNP- 43) polymorphisms are not associated with the risk of T2DM in the studied population.</p><p><strong>Keywords:</strong> Association study, <em>CAPN10</em>,<em> TCF7L2</em>, Type 2 diabetes mellitus, rs11196205, rs3792267</p> Abdollah Gravand, Ali Mohammad Foroughmand, Mehdi Pourmehdi Boroujeni Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181810 Mon, 14 Jan 2019 00:00:00 +0000 New insights into smudge cell percentage in chronic lymphocytic Leukemia: A novel prognostic indicator of disease burden https://www.ajol.info/index.php/ejhg/article/view/181811 <p><strong>Background:</strong> Percentage of smudge cells in CLL patients has recently been reported as a novel prognostic factor.</p><p><strong>Objectives:</strong> To investigate the impact of smudge cells percentage on the clinicolaboratory data of CLL patients and to evaluate the relationship between it and other prognostic factors in CLL.</p><p><strong>Methods:</strong> Ninety adults with CLL were enrolled. Smudge cells percentage was calculated by microscopic evaluation of blood smears. Testing of CD38 expression was done by immunophenotyping and detection of ATM, P53 deletions and trisomy 12 were performed using fluorescent in situ hybridization (FISH)</p><p><strong>Results:</strong> Lower smear cells percentage (&lt;30%) was significantly correlated with age, lymphadenopathy, organomegaly and advanced staging. It was also associated with high TLC, low hemoglobin and platelets count and high absolute and atypical lymphocytic count. Correlation studies with other prognostic factors revealed an association between low smear cells percentage and CD38 expression, short LDT, P53 and ATM deletions. Logistic regression analysis was also done to provide complementary prognostic information identifying the significant independent factors that predict low smear cell percentage.</p><p><strong>Conclusion:</strong> low percentage of smudge cells (&lt;30%) could be considered as an adverse prognostic predictor being associated with high risk markers in CLL.</p><p><strong>Keywords:</strong> Smudge cells, CLL</p> Amal Abd El Hamid Mohamed, Nesma Ahmed Safwat Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181811 Mon, 14 Jan 2019 00:00:00 +0000 Detection of antimicrobial resistance genes of <i>Helicobacter pylori</i> strains to clarithromycin, metronidazole, amoxicillin and tetracycline among Egyptian patients https://www.ajol.info/index.php/ejhg/article/view/181812 <p><strong>Background:</strong> Antibiotic resistance of <em>Helicobacter pylori</em> (<em>H. pylori</em>) treatment is on the rise, and is affecting the efficacy of current used therapeutic regimens.</p><p><strong>Aim:</strong> We aimed to enhance the understanding of antimicrobial resistance rates of <em>H. pylori</em> strains recovered from patients at Theodor Bilharz Research Institute Hospital in Egypt, as a mandatory step before starting treatment.</p><p><strong>Subjects and methods:</strong> Mutant genes conferring metronidazole, amoxicillin, clarithromycin, and tetracycline resistance were detected in 60 <em>H. pylori</em> strains recovered from patients who underwent upper endoscopic examination. Patients were considered to be infected with <em>H. pylori</em> when rapid urease test and detection of 16S<em> rRNA</em> in gastric biopsies recorded positive. Molecular detection of resistant genes to metronidazole (<em>rdx</em> gene) and amoxicillin (<em>pbp1A</em> gene) was carried out by conventional PCR followed by sequencing of PCR products. While detection of <em>23S rRNA</em> gene conferring clarithromycin resistance and detection of <em>16S rRNA</em> mutation gene conferring tetracycline resistance were carried out by realtime PCR.</p><p><strong>Results: </strong> <em>H. pylori</em> resistance rates to metronidazole, and amoxicillin were 25% and 18.3% respectively. While for clarithromycin and tetracycline, point mutations in 23S <em>rRNA</em> types <em>A2142G</em> and<em> A2143G</em> and in<em> 16S rRNA</em> of <em>H. pylori</em> were assessed by real time PCR assay respectively. Resistance mutant genes were found to be 6.7% of clarithromycin and 1.7% of tetracycline. Combined resistance rates to metronidazole and amoxicillin was (11.6%) followed by metronidazole and clarithromycin (5%), while patterns of clarithromycin and amoxicillin (1.6%), metronidazole, clarithromycin and amoxicillin (1.6%) were revealed.</p><p><strong>Conclusion:</strong> Data concerning antimicrobial resistance genes play an important role in empiric treatment of <em>H. pylori</em> infection. According to our results, <em>H. pylori</em> resistance to metronidazole and amoxicillin was relatively high. Clarithromycin is still a good option for first line anti-<em>H. pylori</em> treatment. Combined resistant strains are emerging and may have an effect on the combination therapy.</p><p><strong>Keywords:</strong> <em>H. pylori</em>, Antimicrobial resistance, Gene mutations,<em> Rdx</em> gene, Clarithromycin resistance, Tetracycline resistance</p> Manal Diab, Ahmed El-Shenawy, Maged El-Ghannam, Dalia Salem, Moustafa Abdelnasser, Mohamed Shaheen, Mahmoud Abdel-Hady, Effat El-Sherbini, Mohamed Saber Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181812 Mon, 14 Jan 2019 00:00:00 +0000 Genetic study of the <i>NOTCH3</i> gene in CADASIL patients https://www.ajol.info/index.php/ejhg/article/view/181814 <p><strong>Background:</strong> Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic, hereditary, neurological syndrome characterized by small vessel disease (SVD), stroke, vascular cognitive impairment and dementia. It is caused by mutations in the <em>NOTCH3 </em> gene, affecting the number of cysteines in the extracellular domain of the receptor, causing protein misfolding and receptor aggregation. The pathogenic role of cysteine-sparing <em>NOTCH3</em> missense mutations in patients with typical clinical CADASIL syndrome is unknown. No therapies are available for this condition.</p><p><strong>Objective:</strong> Genetic study of the <em>NOTCH3</em> gene in CADASIL patients who were referred to the Fazeli-Sanati Genetics Laboratory.</p><p><strong>Subjects and methods:</strong> Peripheral blood samples were collected from 10 CADASIL patients to extract genomic DNA. DNA sequences of exons 2–8, 11–12 and 18–19, where <em>NOTCH3</em> mutations are typically located; were amplified by using PCR and analyzed by direct sequencing.</p><p><strong>Results:</strong> 11<em> NOTCH3</em> exons were analyzed. Homozygous IVS7 + 15A&gt;G mutation were found in five patients, Homozygous IVS7 + 16A&gt;G mutation in one patient, Heterozygous for the Pro109Thr and Pro203His mutations in one patient, which were not reported previously. Heterozygous C395R and R153C mutations were found in two patients. One of the patients has no mutation in 11 analyzed <em>NOTCH3</em> exons.</p><p><strong>Conclusion:</strong> We found four novel mutations (P109T, P203H, IVS7 + 15A&gt;G and IVS7 + 16A&gt;G) and 2 reported <em>NOTCH3</em> mutations. Exon 4 and Intron 7 are hotspots in the patients we examined with the <em>NOTCH3</em> mutations. These findings broaden the mutational spectrum of CADASIL.</p><p><strong>Keywords: </strong> CADASIL, <em>NOTCH3</em>, Mutation, Exon</p> Seyedeh Parisa Chavoshi Tarzjani, Seyed Abolhassan Shahzadeh Fazeli, Mohammad Hossein Sanati, Zahra Mirzayee Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181814 Mon, 14 Jan 2019 00:00:00 +0000 Cantu syndrome in an Egyptian child https://www.ajol.info/index.php/ejhg/article/view/181816 <p>We report a 3 month old female, third in order of birth of non consanguineous Egyptian parents with the typical features of Cantu syndrome including coarse features, low frontal hairline, hairy forehead, broad flat nasal bridge, anteverted nares, long philtrum, small low set ears, high arched palate, excess hair on the cheeks, short neck and excess hair over extremities and back. The patient had patent ductus arteriosus ligation, and mild pulmonary hypertension. Our patient has an affected mother which is consistent with autosomal dominant inheritance.</p><p><strong>Keywords:</strong> Cantu syndrome, Hypertrichosis, Coarse features</p> Rabah M. Shawky, Radwa Gamal Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181816 Mon, 14 Jan 2019 00:00:00 +0000 Asymptomatic hemochromatosis case with HFE c.1007-47G>A, c.340+4T>C heterozygous mutations and alpha globin -3.7 kb deletion https://www.ajol.info/index.php/ejhg/article/view/181817 <p><strong>Background:</strong> Hereditary hemochromatosis is a disease associated with iron deposition which is caused by the mutations in ‘‘hereditary Fe (iron)” (HFE) gene.</p><p><strong>Case:</strong> The 16-year-old male patient was diagnosed with hereditary hemochromatosis after c.1007-47G&gt;A heterozygous c.340+4 T&gt;C heterozygous mutations were detected in HFE gene analysis after a suspicion of hemochromatosis due to increase of hemoglobin value from 14.8 g/dL to 16.8 g/dL and the level of ferritin from 68 ng/ml to 300 ng/ml in routine check-up controls in two-years period. In addition, due to low mean corpuscular volume (MCV) (76 fL), and mean corpuscular hemoglobin (MCH) (26 pg) levels, gene mutation analysis was carried out and the patient was also shown to carry a thalassemia -3.7 deletions.</p><p><strong>Conclusion:</strong> Early diagnosis of hemochromatosis is important in terms of prognosis and morbidity. We aimed to emphasize that we can easily diagnose the disease by performing genetic analysis in cases with suspected hemochromatosis even they have no complaints.</p><p><strong>Keywords:</strong> Hemochromatosis, HFE gene mutation, Alpha globulin deletion</p> Vesile Deniz Çelik, Betul Orhan Kiliç, Yasemin Ardıçoğlu Akışin, Fatma Ajlan Tükün, Nejat Akar Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181817 Mon, 14 Jan 2019 00:00:00 +0000 The clinical, cytogenetics and molecular characterization of inverted duplication/deletion of chromosome 8p in a boy with mental and motor retardation: Genotype-phenotype correlation in a case report https://www.ajol.info/index.php/ejhg/article/view/181819 <p><strong>Background:</strong> Rearrangements that occur mainly through the non-allelic homologous recombination (NAHR) during maternal meiosis in short arms of chromosome 8 is relatively associated with various clinical spectrum.</p><p><strong>Aim:</strong> The objective of this study was to report cytogenetics and molecular characterization of a mental and motor retarded boy with short arm of chromosome 8 rearrangements [invdupdel(8p)] in this current case report. Subjects and methods: We report an 11-year-old boy with scoliosis, intellectual disability, mental-motor retardation and characteristic facial features. Agenesis of corpus callosum was detected with brain Magnetic Resonance Imaging (MRI) analysis. Derivative chromosome 8 structure was identified after conventional cytogenetics – karyotype analysis, Multiplex Ligation-Dependent Probe Amplification (MLPA) and Microarray-based Comparative Genomic Hybridization (aCGH) techniques. Genotype-phenotype correlation in the current proband case will be discussed.</p><p><strong>Results:</strong> Case was diagnosed as 46, XY, der (8), del (8) (p23.1) invdup (8) (p11.1-p23.1) by using advanced comparable techniques. Subtelomeric MLPA analysis showed deletion of FBXO25 gene which is located at 8p23.3 locus and FISH with subtelomeric probes for 8p shows also only deleted region. The microarray- CGH profilling showed 7,9 mb deletion for 8p23.1 and 31 mb duplication for 8p11.1 locuses.</p><p><strong>Conclusion:</strong> Results from the current case emphasized that the cases with clinical manifestations of such disorders extremely need to be examined by combined comparable genetics techniques such as; karyotyping, FISH, MLPA and chromosomal microarray for the accurate phenotype – genotype correlation.</p><p><strong>Keywords:</strong> Chromosomal rearrangement, Corpus callosum, Invdupdel(8p)<br />Array-CGH, MLPA</p> Fatma Silan, Romyla Bourouba, Taner Karakaya, Onur Yildiz, Baris Paksoy, Mine Urfali, Ozturk Ozdemir Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181819 Mon, 14 Jan 2019 00:00:00 +0000 Removal notice to ‘‘An Egyptian patient with Schwartz-Jampel syndrome type I and new ocular findings” [Egypt J Med Hum Genet 18 (2017) 393–396] https://www.ajol.info/index.php/ejhg/article/view/181820 <p>This article has been removed: please see Elsevier Policy on Article Withdrawal (<a href="https://www.elsevier.com/about/our-business/policies/article-withdrawal">https://www.elsevier.com/about/our-business/policies/article-withdrawal</a>).</p><p>This article was removed at the request of the authors due to developments in the reported case.</p> Solaf M. Elsayed, Radwa Gamal Copyright (c) https://www.ajol.info/index.php/ejhg/article/view/181820 Mon, 14 Jan 2019 00:00:00 +0000