C634R mutation of the protooncongene RET and molecular diagnosis in multiple endocrine neoplasia type 2 in a large Moroccan family

Abstract

Multiple endocrine neoplasia (MEN) 2A is an inherited disease characterized by the development of medullary thyroid carcinoma (MTC), pheochromocytoma and/or hyperparathyroïdism. It has been shown to be associated with germline mutations in the RET proto-oncogene. Direct DNA testing, therefore allows the identification of subjects with asymptomatic MEN 2A who can be offered prophylactic thyroidectomy and biochemical screening as preventive measures. DNA analysis of RET exon 8, 10, 13, 14, 15 and 16 was performed by direct sequencing of PCR product on automated sequencer and or PCR-digestion. In this report, we describe a MEN2A family witch initially seemed a sporadic case of MTC. We first characterized the C634R RET mutation in the index and then we identified 3 carriers who developed the disease and 3 young carriers who were apparently asymptomatic. A genetic counselling and the management of the carriers were proposed. This study confirmed that genetic testing ; in order to detect gene carriers is technically possible in Morocco. This will contribute to the definition of a national policy of this cancer control.