桑格测序
外显子组测序
外显子组
复合杂合度
遗传学
医学遗传学
先证者
肥胖
基因组学
医学
生物
生物信息学
儿科
突变
基因
基因组
内科学
作者
Pingping Wang,Suhong Yang,Qiong Zhang,Jianmei Zhang,Yan Zhang,Dan Li
出处
期刊:PubMed
日期:2023-04-10
卷期号:40 (4): 473-477
标识
DOI:10.3760/cma.j.cn511374-20210411-00321
摘要
To explore the clinical phenotype and genetic etiology of a child with early-onset severe obesity.A child who presented at the Department of Endocrinology, Hangzhou Children's Hospital on August 5, 2020 was selected as the study subject. Clinical data of the child were reviewed. Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing (WES) was carried out on the child. Candidate variants were verified by Sanger sequencing and bioinformatic analysis.This child was a 2-year-and-9-month girl featuring severe obesity with hyperpigmentation on the neck and armpit skin. WES revealed that she has harbored compound heterozygous variants of the MC4R gene, namely c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp). Sanger sequencing confirmed that they were respectively inherited from her father and mother. The c.831T>A (p.Cys277*) has been recorded by the ClinVar database. Its carrier frequency among normal East Asians was 0.000 4 according to the 1000 Genomes, ExAC, and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as pathogenic. The c.184A>G (p.Asn62Asp) has not been recorded in the ClinVar, 1000 Genomes, ExAC and gnomAD databases. Prediction using IFT and PolyPhen-2 online software suggested it to be deleterious. Based on the guidelines from the ACMG, it was determined as likely pathogenic.The c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp) compound heterozygous variants of the MC4R gene probably underlay the early-onset severe obesity in this child. Above finding has further expanded the spectrum of MC4R gene variants and provided a reference for the diagnosis and genetic counseling for this family.
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