错义突变
遗传学
外显子组测序
促性腺激素减退症
遗传咨询
桑格测序
无义突变
胡说
生物
突变
外显子
生物信息学
医学
基因
内分泌学
激素
作者
Tian Wang,Wu Ren,Fangfang Fu,Hairong Wang,Yan Li,Jie Duan
出处
期刊:Heliyon
[Elsevier]
日期:2024-01-01
卷期号:10 (1): e23272-e23272
标识
DOI:10.1016/j.heliyon.2023.e23272
摘要
CHARGE syndrome is a congenital hereditary condition involving multiple systems. Patients are easily misdiagnosed with idiopathic hypogonadotropic hypogonadism (IHH) due to the overlap of clinical manifestations. An accurate clinical diagnosis remains challenging when the predominant clinical manifestation resembles hypogonadotropic hypogonadism.This original research is conducted based on the genetic finding and analysis of clinical cases. Whole-exome sequencing (WES) and in-silico analyse were performed on two sisters to investigate the pathogenesis in this family. Homology modelling was conducted to evaluate structural changes in the variants.WES and Sanger sequencing revealed two siblings carrying a nonsense mutation (NM_017780.4: c.115C > T) in exon 2 of CHD7 inherited from a mildly affected mother and a missense mutation (NM_015295.3: c.2582T > C) in exon 20 of SMCHD1 inherited from an asymptomatic father. The nonsense mutation in CHD7 was predicted to generate nonsense-mediated decay, whereas the missense mutation in SMCHD1 decreased protein stability.We identified digenic CHD7 and SMCHD1 mutations in IHH-associated diseases for the first time and verified the synergistic role of oligogenic inheritance. It was also determined that WES is an effective tool for distinguishing diseases with overlapping features and establishing a molecular diagnosis for cases with digenic or oligogenic hereditary disorders, which is beneficial for timely treatment, and family genetic counseling.
科研通智能强力驱动
Strongly Powered by AbleSci AI