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Egyptian Journal of Medical Human Genetics

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A germline RET proto-oncogene mutation in multiple members of an Arab family with variable onset of MEN type 2A-associated clinical manifestations

Makia Marafie, Ibrahim Suliman, Mohammed Dashti, Abdulla Redha, Abdulrahman Alshati

Abstract


Background: Multiple endocrine neoplasia type 2A (MEN2A) is a rare cancer associated-syndrome, inherited in an autosomal dominant fashion and caused by germline mutation in RET proto-oncogene. Clinical diagnosis depends on the manifestation of two or more certain endocrine tumors in an individual, such as medullary thyroid carcinoma, pheochromocytoma, and parathyroid adenoma or hyperplasia. Prophylactic total thyroidectomy with central neck lymph node dissection is mandatory for mutation carriers, with periodic monitoring of the other concerned organs.
Subjects and methods: We have screened 27 individuals from a large Arab family with multiple affected members. Mutational screening involved the hotspot regions in the most commonly implicated exons 10 and 11 of RET proto-oncogene using PCR amplification of the coding and the flanking intronic regions followed by the Sanger sequencing. We aimed for confirmation of the clinical diagnosis and identification of at-risk asymptomatic mutation carriers.
Results: A pathogenic variant c.1901G> T (p.Cys634Phe), in exon 11 of RET proto-oncogene was identified in 15 members of different ages.
Conclusion: Genetic counseling plays a key role in the management of such high-risk families and hence helps in avoiding or reducing disease recurrence in their future generations.




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