Siham Chafai Elalaoui
Génomique et Epidémiologie Moléculaire des Maladies Génétiques (G2MG), Centre GENOPATH, Faculté de Médecine et de Pharmacie, Mohammed V University in Rabat, Rabat, Maroc; Département de Génétique Médicale, Institut National d´Hygiène, Rabat, Morocco
Nawfal Fejjal
Service de Chirurgie Plastique Pédiatrique, Hôpital des Enfants, Centre Hospitalier Universitaire Ibn Sina, Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Maroc
Yun Li
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany; Institute of Human Genetics, University Hospital Cologne, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
Holger Thiele
Cologne Center for Genomics, University of Cologne, Cologne, Germany
Janine Altmüller
Cologne Center for Genomics, University of Cologne, Cologne, Germany
Soukaina Guaoua
Génomique et Epidémiologie Moléculaire des Maladies Génétiques (G2MG), Centre GENOPATH, Faculté de Médecine et de Pharmacie, Mohammed V University in Rabat, Rabat, Maroc
Peter Nürnberg
Cologne Center for Genomics, University of Cologne, Cologne, Germany
Bernd Wollnik
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany; Institute of Human Genetics, University Hospital Cologne, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
Abdelaziz Sefiani
Génomique et Epidémiologie Moléculaire des Maladies Génétiques (G2MG), Centre GENOPATH, Faculté de Médecine et de Pharmacie, Mohammed V University in Rabat, Rabat, Maroc; Département de Génétique Médicale, Institut National d´Hygiène, Rabat, Morocco
Ilham Ratbi
Génomique et Epidémiologie Moléculaire des Maladies Génétiques (G2MG), Centre GENOPATH, Faculté de Médecine et de Pharmacie, Mohammed V University in Rabat, Rabat, Maroc; Département de Génétique Médicale, Institut National d´Hygiène, Rabat, Morocco
Abstract
Split-hand foot malformation (SHFM) is a clinically heterogeneous congenital limb defect affecting predominantly the central rays of hands and/or feet. The clinical expression varies in severity between patients as well between the limbs in the same individual. SHFM might be non-syndromic with limb-confined manifestations or syndromic with extra-limb manifestations. Isolated SHFM is a rare condition with an incidence of about 1 per 18,000 live born infants and accounts for 8-17% of all limb malformations. To date, many chromosomal loci and genes have been described as associated with isolated SHFM, i.e., SHFM1 to 6. SHFM6 is one of the rarest forms of SHFM, and is caused by mutations in WNT10B gene. Less than ten pathogenic variants have been described. We have investigated a large consanguineous Moroccan family with three affected members showing feet malformations with or without split hand malformation phenotypes. Using an exome sequencing approach, we identified a homozygous nonsense variant p.Arg115* of WNT10B gene retaining thereby the diagnosis of SHFM6. This homozygous nonsense mutation identified by exome sequencing in a large family of split hand foot malformation highlights the importance of exome sequencing in genetically heterogeneous entities.
