目的： 分析1例多发性内分泌腺瘤2A（multiple endocrine neoplasia 2A, MEN2A）患者及其家系的临床特征,同时复习相关文献进行综合探讨。方法： 先证者为女性,33岁,收集其家系的临床资料,并采集先证者及家庭成员的外周血,抽提基因组DNA,对RET基因编码区进行Sanger测序,并以300名不相关的健康志愿者作为对照,对突变的基因进行致病性及保守性分析。结果： 先证者的血生化检测结果显示,血钙、甲状旁腺激素（parathyroid hormone,PTH）和降钙素水平升高,分别为3.25 mmol/L、1 252 ng/L和37.24 ng/L;术后病理检查结果证实其存在单侧甲状旁腺腺瘤和甲状腺髓样癌（medullary thyroid carcinoma, MTC）。Sanger测序显示,先证者RET基因11号外显子存在杂合错义突变c.1901G>A,导致p.Cys634Tyr,该致病基因来自先证者母亲,而其健康姐姐及对照者均未发现相同突变。结论： 本研究中先证者为RET基因11号外显子错义突变c.1901G>A导致的MEN2A。MEN2A的确诊依靠对RET基因突变的检测。早期手术干预是该病最佳的治疗手段,术后对MTC复发情况进行随访是评估MEN2A患者预后的关键。已有RET基因突变的先证者应对其胎儿进行致病基因筛查,从而进行早期干预以降低MEN2A的发病率和死亡率。

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 The genomic DNA was extracted from peripheral blood withdrawn from the proband and family members, and coding region of RET gene was analyzed by Sanger sequencing.Three hundred unrelated healthy volunteers were enrolled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.