不同基因突变方式的两个多发性内分泌腺瘤病2A型家系相关临床特征比较

A comparison of clinical characteristics between 2 pedigrees of multiple endocrine neoplasia type 2A with different RET mutations

通过对多发性内分泌腺瘤病2A型（MEN2A）家系成员进行DNA测序,发现两个MEN2A家系RET原癌基因存在不同的基因突变方式,其中家系1的基因突变为一种新的突变类型（第11外显子杂合突变1893～1895delCGA）;虽然突变方式不同,但临床表现相似,均为中年发病,大部分以双侧肾上腺嗜铬细胞瘤起病;有不同程度的甲状腺异常,血降钙素升高伴或不伴甲状腺出现占位性病变,或已确诊为甲状腺髓样癌（MTC）;部分成员血甲状旁腺激素（iPTH）升高,但尚缺少诊断甲状旁腺功能亢进症（HPT）的其他证据.

Multiple endocrine neoplasia type 2A （MEN2A） is a hereditary syndrome. Here, two different RET proto-oncogen mutation were identified from family members of two MEN2A pedigrees by genetic screening. One RET mutations were found at codons 1893 and 1895 in exon 11 （1893-1895delCGA） from pedigree 1, which is a novel mutation, the other occurs at codon 634 （Cys634Arg） in exon 11 from pedigree 2. However, the clinical characteristics were similar in the patients of the two pedigrees. All the patients were in middle-age at onset. Most of them were firstly diagnosed with bilateral adrenal pheochromocytoma with different degrees of thyroid abnormalities （elevated serum calcitonin with or without thyroid mass, or had been diagnosed with medullary thyroid carcinoma）. Some family members were with elevated serum parathyroid hormone but with no other evidences for hyperparathyroidism.