Identification and functional analysis of a novel variant of CHD23 gene in a Chinese pedigree affected with Non-syndromic autosomal recessive deafness 12.
10.3760/cma.j.cn511374-20250514-00290
- Author:
Litao QIN
1
;
Zengguo REN
;
Meiying WANG
;
Tingting SHI
;
Xin CHEN
;
Qian ZHANG
;
Guiyu LOU
;
Shixiu LIAO
;
Li WANG
Author Information
1. Medical Genetics Institute of Henan Province, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan 450003, China. wanglily@zzu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Humans;
Pedigree;
Male;
Female;
Asian People/genetics*;
Cadherins/genetics*;
Exome Sequencing;
Deafness/genetics*;
Mutation;
China;
Adult;
Cadherin Related Proteins;
Hearing Loss, Sensorineural/genetics*;
East Asian People
- From:
Chinese Journal of Medical Genetics
2025;42(12):1490-1495
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To analyze a Chinese pedigree affected with Non-syndromic autosomal recessive deafness type 12 (NFNB12), validate the function of candidate variants, and explore the underlying mechanisms.
METHODS:A NFNB12 pedigree presented at Henan Provincial People's Hospital in February 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing of the pedigree members. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine the level of mRNA transcription in the peripheral blood samples from the pedigree members, and protein expression was evaluated with Western blotting assay. This study was approved by Medical Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2019-134).
RESULTS:WES analysis revealed that the proband has harbored homozygous c.6688delG (p.Ala2230Profs*4) variant of the CDH23 gene, for which both parents were identified as heterozygous carriers. RT-PCR analysis demonstrated the sole presence of the variant mRNA in the proband, and both the variant and wild-type mRNAs in both parents. Furthermore, Western blotting analysis indicated that the proband had exclusively expressed the truncated CDH23 protein, while both the normal and truncated forms of the protein were noted in her parents.
CONCLUSION:The c.6688delG (p.Ala2230Profs*4) variant of the CDH23 gene probably underlay the pathogenesis of NFNB12 in this pedigree. The loss of function of the CDH23 gene resulting from this variant is not related with nonsense-mediated mRNA decay, but rather production of a truncated protein. Above finding has not only enriched the mutational spectrum of the CDH23 gene and offered a method for investigating the function of its variants using peripheral blood samples, but also delineated the molecular basis for the loss of function, which has provided crucial evidence for genetic counseling and prenatal diagnosis for this family.
