Clinical features and analysis of a case with Brain small vessel disease 1 with ocular anomalies due to variant of COL4A1 gene
10.3760/cma.j.cn511374-20240521-00301
- VernacularTitle:COL4A1基因变异致脑小血管病伴眼部异常1例患儿的遗传学分析
- Author:
Chunxiao HAN
1
;
Lulu YAN
;
Yuxin ZHANG
;
Haibo LI
Author Information
1. 宁波大学附属妇女儿童医院出生缺陷综合防治中心，宁波 315000
- Publication Type:Journal Article
- Keywords:
Brain small vessel disease;
COL4A1 gene;
Whole exome sequencing
- From:
Chinese Journal of Medical Genetics
2025;42(4):495-499
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic etiology of a child with brain small vessel disease 1 with ocular anomalies.Methods:A child who was adwstted to Ningbo Women and Children′s Hospital on May 28, 2022, was selected for the study. Clinical data were collected, and peripheral blood samples from the child and her parents were obtained for genomic DNA extraction. Whole exome sequencing (WES) was performed to screen for pathogenic variants. Candidate variants were validated via Sanger sequencing and subjected to bioinformatic analysis. This study was approved by the Medical Ethics Committee of Ningbo Women and Children′s Hospital (Ethics No. EC2020-048).Results:① The child was a 7-year-old female with a diagnosis of epilepsy. ② WES revealed that she has carried a heterozygous missense variant in the COL4A1 gene: c. 1792G>A (p.Gly598Ser). Sanger sequencing confirmed that her parents both had the wild-type genotype for this variant. Based on American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants, the variant were predicted to be a likely pathogenic (PS2+ PM1+ PM2_Supporting+ PP3). ③ Bioinformatics predicted that amino acid 598 was highly conserved in different species, formed hydrogen bond with Asp599 after becoming Ser598. Conclusion:The heterozygous missense variant of the COL4A1 gene c. 1792G>A (p.G598S) could be the pathogenic cause of this child with Brain small vessel disease 1 with ocular anomalies.
