Abstract:

Objective: To analyze the clinical characteristics, gene mutation of a pedigree diagnosed with multiple endocrine neoplasia 2A (MEN2A) and comprehensively review the related literature. Methods: The proband was a 33-year-old female,and the clinical data of the pedigree was collected. The genomic DNA was extracted from peripheral blood withdrawn from the proband and family members, and coding region of RET gene was analyzed by Sanger sequencing.Three hundred unrelated healthy volunteers were enrolled as controls. Pathogenicity and conservativeness analysis were carried on the detected mutant gene. Results: The blood biochemical examination of the proband showed the increased calcium (3.25 mmol/L), parathyroid hormone(1 252 ng/L) and calcitonin (37.24 ng/L) in serum. The presence of unilateral parathyroid adenoma and medullary thyroid carcinoma(MTC) were confirmed by postoperative pathology. Sanger sequen-cing identified that a heterozygous missense mutation in exon 11 of RET gene c.1901G>A in proband led to p.Cys634Tyr. The pathogenic gene came from the mother, while the healthy sister or the controls did not show the same mutation. Conclusions: The proband with MEN2A is caused by a missense mutation in exon 11 of RET gene (c. 1901G> A). The diagnosis of MEN2A depends on the detection of RET gene mutation. Early surgical intervention is the best treatment choice for MEN2A patients. Postoperative follow-up of the recurrence of MTC is the key to assessing the prognosis in MEN2A patients. Screening RET gene mutation in the fetus of proband with RET mutation is necessary, and intervention as early as possible may decrease the incidence and mortality of MEN2A.

Key words: Multiple endocrine neoplasia 2A, Medullary thyroid carcinoma, RET gene, Mutation