A large Chinese pedigree of multiple endocrine neoplasia type 2A with a novel C634Y/D707E germline mutation in exon 11.

The present study identified the clinical features of the largest multiple endocrine neoplasia type 2 (MEN2) A pedigree from China, with a novel double missense mutation (C634Y/D707E). To the best of our knowledge, the D707E mutation has not been identified to date. In the present study, a total of 101 family members who originated from a large pedigree (134 members in total) underwent mutation screening by next-generation sequencing and polymerase chain reaction (PCR) amplification, followed by direct bidirectional DNA sequencing. The clinical features of this pedigree were carefully reviewed retrospectively, and statistical analyses were conducted using SPSS software. A total of 33 (32.67%) carriers were identified to exhibit the C634Y/D707E germline mutation. The mean age of the patients with medullary thyroid carcinoma (MTC) identified by screening was 38.4±16.5 years (n=11; range, 14-65 years). Only 4 patients with pheochromocytoma with a median age of 37 years were identified. No hyperparathyroidism was diagnosed. Persistent or recurrent disease developed in the patients of the present study who underwent inappropriate initial thyroid surgeries that were performed in previous decades (III10, III23, III24, III27 and IV46, as they had undergone two surgeries prior to the present study). A total of 66.70% (6/9) of patients, following thyroidectomy, continued to develop persistent or recurrent disease during the present screening study. In total, 3 patients succumbed to MTC or distant metastasis in the present study. The increase in carcinoembryonic antigen (CEA) levels correlated with the increase in basal serum calcitonin (Ct) levels according to Pearson correlation analysis in patients with MTC without surgery. Ct and CEA levels were also significantly correlated with tumor volumes. To the best of our knowledge, the present study is the first to identify a novel double missense mutation in the largest MEN2A pedigree from China. Additional in-depth study is necessary to elucidate the molecular mechanisms of the D707E mutation and its potential joint effects with the other C634Y mutation in the pedigree of the present study.