Comprehensive characterization of the genetic landscape of familial Hirschsprung's disease
作者机构：Department of Pediatric SurgeryTongji HospitalTongji Medical CollegeHuazhong University of Science and Technology1095 Jiefang AvenueWuhan 430030China Hubei Clinical Center of Hirschsprung's Disease and Allied DisordersWuhan 430030China Department of RadiologyTongji HospitalTongji Medical CollegeHuazhong University of Science and Technology1095 Jiefang AvenueWuhan 430030China
出 版 物：《World Journal of Pediatrics》 (世界儿科杂志（英文版）)
年 卷 期：2023年第19卷第7期
页 面：644-651页
核心收录：
学科分类：1002[医学-临床医学] 100202[医学-儿科学] 10[医学]
基 金：National Natural Science Foundation of China(82071685 to FJX) Clinical Research Pilot Project of Tongji Hospital(2019YBKY026 to FJX) Provincial Key Research and Development Program(2020BCB008 to FJX) Science and Technology Innovation Base Platform(2020DCD006 to FJX) Project of Shenzhen San Ming(SZSM201812055 to FJX).
主 题：Genetic characteristics Hirschsprung's disease Penetrance Recurrence risk Ret proto-oncogene(RET)
摘 要：Background Hirschsprung s disease(HSCR)is one of the most common congenital digestive tract malformations and can cause stubborn constipation or gastrointestinal obstruction after birth,causing great physical and mental pain to patients and their families.Studies have shown that more than 20 genes are involved in HSCR,and most cases of HSCR are sporadic.However,the overall rate of familial recurrence in 4331 cases of HSCR is about 7.6%.Furthermore,familial HSCR patients show incomplete dominance.We still do not know the penetrance and genetic characteristics of these known risk genes due to the rarity of HSCR families.Methods To find published references,we used the title/abstract termsHirschsprungandfamilialin the PubMed data-base and the MeSH termsHirschsprungandfamilialin Web of Science.Finally,we summarized 129 HSCR families over the last 40 years.Results The male-to-female ratio and the percentage of short segment-HSCR in familial HSCR are much lower than in sporadic HSCR.The primary gene factors in the syndromic families are ret proto-oncogene(RET)and endothelin B receptor gene(EDNRB).Most families show incomplete dominance and are relevant to RET,and the RET mutation has 56%pen-etrance in familial HSCR.When one of the parents is a RET mutation carrier in an HSCR family,the offspring s recurrence risk is 28%,and the incidence of the offspring does not depend on whether the parent suffers from HSCR.Conclusion Our findings will help HSCR patients obtain better genetic counseling,calculate the risk of recurrence,and provide new insights for future pedigree studies.
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