Caron P, Attié T, David D, Amiel J, Brousset F, Roger P, Munnich A, Lyonnet S
Service d'Endocrinologie, CHU Rangueil, Toulouse, France.
J Clin Endocrinol Metab. 1996 Jul;81(7):2731-3. doi: 10.1210/jcem.81.7.8675603.
The cosegregation of multiple endocrine neoplasia (MEN) type 2A with Hirschsprung's disease (HSCR), two diseases associated with mutation of the RET proto-oncogene, is infrequent. A 30-yr-old man was referred for screening of MEN 2A. Surgery for HSCR was performed at 4 yr of age. Basal and pentagastrin-stimulated calcitonin levels were abnormal. Histological examination of the thyroid confirmed bilateral medullary thyroid carcinoma. Screening of family members revealed six subjects with medullary thyroid carcinoma or abnormal pentagastrin-stimulated calcitonin test; one had an unilateral pheochromocytoma and two were affected with HSCR. DNA sequence analysis showed a heterozygote C618R mutation in exon 10 of the RET proto-oncogene in the proband and his mother, as well as in second-degree relatives with MEN 2A phenotype or HSCR. In this study, we report on a novel kindred with MEN 2A and HSCR phenotype associated with a point mutation (C618R) in one of the cysteine codons at the extracellular domain of the RET proto-oncogene.
2A型多发性内分泌腺瘤病（MEN）与先天性巨结肠症（HSCR）的共分离现象并不常见，这两种疾病都与RET原癌基因的突变有关。一名30岁男性因筛查2A型MEN前来就诊。他在4岁时接受了HSCR手术。基础及五肽胃泌素刺激后的降钙素水平异常。甲状腺组织学检查确诊为双侧甲状腺髓样癌。对家庭成员的筛查发现6名患有甲状腺髓样癌或五肽胃泌素刺激后降钙素试验异常的受试者；1人患有单侧嗜铬细胞瘤，2人患有HSCR。DNA序列分析显示，先证者及其母亲以及具有2A型MEN表型或HSCR的二级亲属中，RET原癌基因第10外显子存在杂合子C618R突变。在本研究中，我们报告了一个新的家系，其具有2A型MEN和HSCR表型，与RET原癌基因细胞外结构域中一个半胱氨酸密码子的点突变（C618R）相关。
