RESUMO
Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant disorder that can be distinguished as three different syndromes: multiple endocrine neoplasia type 2A (MEN2A), MEN2B and familial medullary thyroid carcinoma (FMTC). This disorder is usually caused by the mutations of the rearranged during transfection protooncogene gene (RET) or the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1). To investigate the genetic cause in a Chinese Han family with MEN2A and the genotype-phenotype correlations, nine members belonging to 3 generations of MEN2A family with 5 affected subjects underwent genetic analysis. Standard GTG-banded karyotype analysis and sequencing of the RET and NTRK1 genes were performed to identify the genetic cause of this family. A heterozygous mutation p.Cys634Arg in the RET gene was identified in 5 patients with MEN2A and one asymptomatic family member. The phenotype of patients was that of classic MEN2A, characterized by medullary thyroid carcinoma and phaeochromocytoma. The clinical features of all cases with RET mutations varied greatly, including onset age of clinical manifestations, severity and comorbidities. Thus, this study not only identified the hereditary nature of the MEN2A in the cases, but also discovered a family member harboring the same p.Cys634Arg mutation, who was unaware of his condition. These finding may provide new insights into the cause and diagnosis of MEN2A and have implications for genetic counseling.