Han Chunxiao, Yan Lulu, Zhang Yuxin, Li Haibo
Comprehensive Prevention and Control Center for Birth Defects, Ningbo Women and Children's Hospital, Ningbo, Zhejiang 315000, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2024 Aug 10;41(8):962-965. doi: 10.3760/cma.j.cn511374-20230607-00348.
To explore the genetic basis for child with CHARGE syndrome.
A child who was diagnosed at Ningbo Women and Children's Hospital on September 29, 2022 was selected as the study subject. Relevant clinical data were collected. The child and her parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis.
The child was found to harbor a de novo c.2972T>C (p.L991S) missense variant of the CHD7 gene, which was detected in neither of her parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PM6+PM2_Supporting+PP2+PP3+PP4). Bioinformatic analysis predicted that amino acid 991 is highly conserved among various species, and a hydrogen bond has formed between Asp993 and the mutant Ser991.
The heterozygous c.2972T>C (p.L991S) missense variant of the CHD7 gene probably underlay the pathogenesis of CHARGE syndrome in this child. Above finding has also enriched the mutational spectrum for CHARGE syndrome.
探讨CHARGE综合征患儿的遗传基础。
选取2022年9月29日在宁波市妇女儿童医院确诊的一名患儿作为研究对象，收集相关临床资料。对该患儿及其父母进行全外显子组测序（WES），并通过Sanger测序和生物信息学分析对候选变异进行验证。
发现该患儿携带CHD7基因的一个新发c.2972T>C（p.L991S）错义变异，其父母均未检测到该变异。根据美国医学遗传学与基因组学学会（ACMG）的指南，该变异被预测可能致病（PM6+PM2_支持+PP2+PP3+PP4）。生物信息学分析预测，氨基酸991在不同物种间高度保守，且Asp993与突变型Ser991之间形成了氢键。
CHD7基因的杂合c.2972T>C（p.L991S）错义变异可能是该患儿CHARGE综合征发病机制的基础。上述发现也丰富了CHARGE综合征的突变谱。
