Genetic analysis of a Chinese pedigree affected with Achromatopsia due to variants of CNGA3 gene and a literature review
10.3760/cma.j.cn511374-20230911-00124
- VernacularTitle:CNGA3基因变异致中国全色盲一个家系的遗传学分析并文献复习
- Author:
Yingwen LIU
1
;
Yuxin ZHANG
;
Lulu YAN
;
Min XIE
;
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 315012
- Keywords:
Achromatopsia;
CNGA3 gene;
Whole exome sequencing
- From:
Chinese Journal of Medical Genetics
2024;41(9):1077-1083
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the molecular basis for a Chinese pedigree affected with Achromatopsia (ACHM).Methods:A pedigree with ACHM which was admitted to the Women and Children′s Hospital of Ningbo University on April 14, 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out for the proband. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. Related literature was reviewed, and clinical and genetic features of Chinese patients with ACHM due to variants of CNGA3 gene were summarized. This study was approved by the Women and Children′s Hospital of Ningbo University (Ethics No. EC2020-048). Results:WES revealed that the proband and his younger brother had both harbored compound heterozygous variants of the CNGA3 gene, namely c. 1190G>T (p.Gly397Val) and c. 2013del (p.Gly672ValfsTer69), which were respectively inherited from their mother and father. The c. 1190G>T was a known pathogenic variant, while the c.2013del was unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 2013del variant was predicted to be likely pathogenic (PM2_Supporting+ PVS1_Moderate+ PM3+ PP4). Literature review has identified 41 CNGA3 gene variants among 43 patients from 38 pedigrees, most of which were missense variants and had located in exon 8. Most patients were males, with nystagmus, photophobia, amblyopia and other symptoms during infancy/childhood as the main clinical manifestations, and there was a lack of genotype-phenotype correlation. Conclusion:The c. 1190G>T (p.Gly397Val) and c. 2013del (p.Gly672ValfsTer69) variants of the CNGA3 gene probably underlay the ACHM in the proband. Discovery of the c. 2013del variant has enriched the mutational spectrum of the CNGA3 gene and provided a basis for genetic counseling and reproduction guidance for this pedigree.
