Abstract:

Objective　Hirschsprung's disease (HSCR) caused by mutations in the endothelin receptor B (EDNRB) gene has been found in many familial cases. This report of familial HSCR was aimed to clarify the relationship between genetic mutations and clinical phenotype by whole exome sequencing (WES). Methods　In April 2021, Guangdong Women and Children Hospital admitted a newborn with HSCR whose mother had a history of megacolon. Peripheral blood samples of the newborn's parents and maternal grandmother were collected, and WES was performed to analyze the genetic genes. The relevant literatures on HSCR and EDNRB gene mutations published on Wanfang, VIP, CNKI, PubMed, and Medline databases till October 2022 were searched and analyzed. Results　WES revealed a heterozygous mutation in EDNRB, c.367delinsTT(p.L123Fter32), in a newborn index case, proband's parents and grandmother. Two carriers with this mutation had clinical symptoms, other two carriers stayed healthy. Based on literature review, 15 related articles containing 25 plausible mutations had been documented. Conclusions　We identified a novel EDNRB mutation, c.367delinsTT(p.L123FTer32), which resulted in a premature stop codon at amino acid position 155 and produced a protein whose functional domains were completely missing. This mutation might be potentially pathogenic for HSCR.

Key words:

Hirschsprung's disease, Whole exome sequencing, EDNRB

摘要：

目的　内皮素受体B（EDNRB）基因突变引起的先天性巨结肠（HSCR）已在许多家族病例中被发现。本文家族性HSCR研究旨在使用全外显子组测序（WES）阐明基因突变与临床表型之间的关系。方法　2021年4月广东省妇幼保健院收治1例HSCR新生儿，其母亲有巨结肠病史，收集新生儿父母、外婆外周血，WES分析遗传基因。检索万方、维普、中国知网、PubMed、Medline数据库截至2022年10月已发表的关于HSCR与EDNRB基因突变的相关文献，并进行分析。结果　在所有家庭成员中发现4名成员携带1个新的c.367delinsTT（p.L123Fter32） EDNRB杂合突变。只有2名成员表现出临床症状，而其他2名成员表现健康。通过检索数据库，检索到15篇相关文献（共报道26个可能致病的突变位点）。结论　新发现EDNRB基因c.367delinsTT（p.L123Fter32）突变，该突变导致第155位氨基酸提前形成终止密码子，产生功能域完全缺失的蛋白质，可能对HSCR具有致病性。

关键词:

先天性巨结肠, 全外显子组测序, 内皮素受体B基因