The Study Of The Clinical Characteristics And RET Proto-oncogene Mutation In 2 Pedigrees Of Multiple Endocrine Neoplasia Type 2A

Objective:Multiple endocrine neoplasia type 2A(MEN2A), which is a subtype of Multiple endocrine neoplasia(MEN), is an autosomal dominant disease. MEN2 includes MEN2 A and MEN2B, and MEN2 A accounts for 60% of MEN2. MEN2 A,as known as Sipple syndrome, is characterized by the presence of medullary thyroid carcinoma(MTC), pheochromocytoma(PHEO)and primary hyperparathyroidism(HPT). The purpose of the present study is to carry out a clinical investigation and to explore the mutations of the RET proto-oncogene of two pedigrees with multiple endocrine neoplasia type 2A(MEN2A) suggested by clinical manifestations.Methods:1?carry out a clinical investigation and analysis the clinical features of two pedigrees with multiple endocrine neoplasia type 2A(MEN2A).2?Genomic DNA was extracted from the peripheral blood lymphocytes in 10 family members of the 2 pedigrees. Then PCR was performed to amplify six exons of the RET proto-oncogene, that is, exon10,11,13,14,15,16 for two probands. PCR products were purified and then were analysed by direct sequence analysis. According to the sites of the gene mutation of two probands, their family members were underwent genetic testing accordingly.Results1. A missense mutation of Cys643Trp in exon 11 of the RET proto-oncogene was detected in the index case and his brother who present with a thyroid mass of pedigree 1. One doubtful patient had died, so could not have the gene analysis. The other family members had not the same mutation.2. Cys634Arg, which is one of the mutation types of the highest incidence, was detected in exon 11 of the RET proto-oncogene in the 2 patients and another family member of pedigree2. The RET mutation gene carrier was detected with a thyroid mass by ultrasound. The other family members had not the same mutation.Conclusion1. The germline mutations of RET proto-oncogene Cys643Trp and Cys634Arg were the disease—causing mutations of the 2 MEN2A families, and the former was relative rare.2. Although the gene mutmions of RET proto—oncogene in the 2 pedigrees were different, The clinical features between them related to their mutations seem similar.3. The mutations was detected in the two families with MEN2A. Direct DNA sequencing analysis can diagnose MEN2A at gene level, which is helpful in clinical management of the disease and in diagnosing earlier in their offspring, early RET mutation analysis should be performed routinely in all MEN2A, and screening methods may be used in analyzing family members at risk.