Endothelin-B receptor mutations in patients with isolated Hirschsprung disease from a non-inbred population
Endothelin-B receptor mutations in patients with isolated Hirschsprung disease from a non-inbred population
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DOI：
10.1093/hmg/5.3.351
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发表时间：
1996-03-01
影响因子：
3.5
通讯作者：
Ballabio, A
中科院分区：
文献类型：
--
作者：
Auricchio, A;Casari, G;Ballabio, A
先天性巨结肠症（HSCR），或无神经节巨结肠，是先天性肠梗阻的最常见原因，已发现分别在10号和13号染色体上有两个不同的基因座与HSCR紧密连锁。最近，在几名HSCR患者中发现了染色体10q11.2上RET原癌基因的突变，此外，在受HSCR和相关异常影响的近交门诺家族中发现了染色体13 q22上内皮素-B受体（EDNRB）基因的错义突变，证明EDNRB参与HSCR发病机制，为了测试EDNRB基因的突变是否可以解释来自非近交系人群的患者中的先天性巨结肠，我们分析了来自17名意大利血统的HSCR先证者的DNA样本，我们已经鉴定了两种新的EDNRB突变：在散发病例中的错义突变，S305 N，其导致丝氨酸变为天冬酰胺，破坏了推定的磷酸化位点;在一个家族性病例中，N3781的单核苷酸缺失，导致截短的蛋白质，这两种突变都在一个健康的父母中发现，这些数据证实了EDNRB参与HSCR发病机制，并证明EDNRB突变可能导致非近交群体中的HSCR疾病。
Hirschsprung disease (HSCR), or aganglionic megacolon, is the most common cause of congenital intestinal obstruction, Two different loci have been found to be tightly linked to HSCR on chromosomes 10 and 13, respectively, Recently, mutations in the RET protooncogene on chromosome 10q11.2 were identified in several HSCR patients, In addition, a missense mutation in the endothelin-B receptor (EDNRB) gene on chromosome 13q22 was found in an inbred Mennonite kindred affected by HSCR and associated abnormalities, demonstrating the involvement of EDNRB in HSCR pathogenesis, To test whether mutations in the EDNRB gene could account for Hirschsprung in patients from non-inbred populations, we analysed DNA samples from 17 probands of Italian origin with HSCR, We have identified two novel EDNRB mutations: a missense mutation in a sporadic case, S305N, which leads to a change of a serine to an asparagine, disrupting a putative phosphorylation site; and a single nucleotide deletion in a familial case, N3781, resulting in a truncated protein, Both mutations were found in one of the healthy parents, and neither of these mutations were found in any of the normal individuals tested, These data confirm the involvement of EDNRB in HSCR pathogenesis and demonstrate that EDNRB mutations could contribute to HSCR disease in non-inbred populations.