RET proto-oncogene mutation analysis in a pedigree with multiple endocrine neoplasia 2A

Abstract

Objective To discuss the clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN ) 2A, and report the mutation of the RET proto-oncogene in a pedigree of three patients with MEN 2A.Methods Bilateral adrenalectomy was performed on two of the three patients with hypertension and bilateral adrenal-conserving adrenal pheochromocytoma resection was performed on the other patient. All three patients were treated by total thyroidectomy and neck lymphadenectomy. Twelve family members were recruited to the study. Peripheral blood was collected and total genomic DNA was prepared for polymerase chain reaction (PCR). PCR products of exon 10 and exon 11 of the RET proto-oncogene were purified and a direct DNA sequence analysis was performed.Results The pathological diagnosis of the specimens was bilateral adrenal pheochromocytoma and medullary thyroid carcinoma in all the three patients. There was no tumor recurrence or distant metastasis after 1.5 - 5 years of follow-up. A missense mutation of TGC (Cys)to CGC (Arg) at codon 634 in exon 11 of the RET proto-oncogene was detected in all three patients. Genetic screening identified two mutation carriers in the other members of this pedigree.ConclusionGenetic mutation screening and surgical intervention may be helpful to the members of high-risk families. Key words: Multiple endocrine neoplasia 2A; Pheochromocytoma; Medullary thyroid carcinoma; RET proto-oncogene ; Mutation