Screening of the RET Proto-oncogene in Families with Multiple Endocrine Neoplasia Type 2 in Algeria

Abstract

The MEN 2 is a hereditary disorder of dominant autosomal inheritance with complete penetrance associated with germeline RET gene mutations a genetic marker of MTC. The systematic analysis of this gene in any MTC or suspiscion of MEN2A allows for the presymptomatic diagnosis of familial forms. Specific and early treatment, by a surgery cure, of related with genetic risk at an early clinicopathological stage allows a fit treatment, the only guarantee. Three index cases with endocrine neoplasia were hospitalized at the Department of Endocrinology: Two patients 36 years old and 44 years old for exploration and management of bilateral adrenal pheochromocytoma and the other patient aged 40 years old to support a medullary thyroid carcinoma. The three patients underwent endocrine and morphological exploration seeking MEN 2a. The three patients had primary hyperparathyroidism by adenoma, MTC and pheochromocytoma. Direct sequencing of exons in three index cases revealed a mutation at codon 634 in exon 11 of the RET gene with two types of mutations: A transition TgC in the heterozygous state transforming cysteine to arginine (C634R) in the first and third family (2/3 of the cases studied); A transition G gA in the heterozygous state changing the cysteine to tyrosine (C634Y) in the second group (1/3 of the cases studied). Phenotypic and genotypic correlation was found. The extended to members of the three families (siblings, parents and direct and collateral descendants) survey has been accepted by 11 subjects. 5 of them will carry the familial mutation (45.5% of subjects). The clinical and paraclinical found no manifestation of MEN 2 out of MTC. Total thyroidectomy and central neck dissection were indicated for them. The MEN2A syndromic disorders are serious multi-cancerous conditions. Their diagnosis is based on the recognition of their family character, and on exploration highlighting various endocrine abnormalities. Confirmation by the genetic study of RET gene enables a presymptomatic screening and early therapeutic care in related.