Clinical and genetic analysis of a patient with Dent disease due to hemizygous variant of the CLCN5 gene
10.3760/cma.j.cn11374-20241231-00696
- VernacularTitle:CLCN5基因半合子变异致Dent病1例患儿的临床及遗传学分析
- Author:
Fengxun LIU
1
;
Cien WEI
1
;
Dongwei LIU
1
Author Information
1. 郑州大学第一附属医院肾脏内科医学部，中西医结合肾病科，郑州 450052
- Publication Type:Journal Article
- Keywords:
CLCN5 gene;
Dent disease;
X-linked recessive inheritance;
Genetic variant
- From:
Chinese Journal of Medical Genetics
2025;42(4):469-473
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical features and molecular etiology of a patient with Dent disease due to variant of CLCN5 gene. Methods:A male patient with Dent disease diagnosed at the First Affiliated Hospital of Zhengzhou University in September 2023 was selected as the study subject. Clinical data of the patient were collected. Whole exome sequencing (WES) was carried out for the patient and his family members. Pathogenicity of candidate variant was verified by Sanger sequencing and bioinformatic analysis. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. KS-2018-KY-36).Results:The patient, a 15-year-old male, was admitted due to proteinuria and hematuria. Ultrasonography showed diffuse echogenic changes in both kidneys. Renal biopsy revealed structural dysfunction of renal tubules. Electron microscopy revealed minor tubular and glomerular lesions. The patient was found to harbor a hemizygous c. 701dupA (p.Y234Ter) variant of the CLCN5 gene, which was derived from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+ PM2_Supporting). Bioinformatic analysis using multiple software predicted the deleterious effect of the variant. Conclusion:The hemizygous c.701dupA (p.Y234Ter) variant of the CLCN5 gene probably underlay the pathogenesis of Dent disease in this patient. Above finding has enriched the mutational spectrum of the CLCN5 gene.
