目的提高对多发性内分泌腺瘤2型(multiple endocrine neoplasia 2, MEN2)的诊断和预测诊断水平。方法对临床已诊断首发症状为嗜铬细胞瘤的一个家族内两姐妹患者进行RET(外显子10～16)、VHL( 外显子1～3)、 SDHD(外显子1～4)、SDHB(外显子1～8) 及SDHC(外显子1～6) 基因测序。发现两患者均有RET基因634号核酸发生突变,并对其家族其他成员的RET基因进行测序。结果其家族内共有5例患者均有RET基因634号突变(TGC 突变为 CGC),导致其氨基酸编码由半胱氨酸变为精氨酸。其中2例先为临床诊断然后基因诊断,1例先由基因诊断然后临床诊断,2例(均为儿童,分别为6岁及7岁)为基因诊断,目前尚未发病。其中3例行腹腔镜双侧肾上腺肿瘤切除术,病理确诊为双侧嗜铬细胞瘤;1例行甲状腺切除术,病理诊断为甲状腺髓样癌。结论对于多发性内分泌多发肿瘤2A型患者及其家族成员行基因检查不仅可以作为确诊手段,更可以作为无症状者的预测诊断途径。

Objective By gene sequence ,biochemical and imaging testing, we introduce the diagnosis ,especially the predictive diagnosis of MEN2a. Methods Peripheral blood from 2 patients who were sisters presenting pheochromocytoma as the first manifestation of disease was tested for mutations of RET(exon 10 ,11, 12,13,14,15,16), VHL( exon 1 to 3), SDHD(exon 1 to 4), SDHB(exon 1 to 8) and SDHC(exon 1 to 6) by means of genomic polymerase chain reaction (PCR) amplification and DNA sequencing. The mutation affected RET proto-oncogene codon 634 and caused a cysteine to arginine substitution. Then we sequenced the other family members’ RET gene exon 11. Results We have detected point mutation in 5 MEN 2A patients in a MEN 2A family at codon 634 (TGC to CGC) in RET exon 11 which caused a cysteine to arginine substitution. Three of them were diagnosed as having bilateral adrenal pheochromocytomas by pathological examination and bilateral tumor in thyroid gland by ultrasound study. One patient underwent bilateral thyroidectomy and pathological examination showed medullary thyroid carcinoma. Conclusions The identification of a DNA alteration in the MEN2A gene will permit predictive diagnosis. Molecular testing of individuals at risk in these MEN 2A families is considered part of the standard management for at-risk family members.