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Updated: Jul 17, 2025
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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
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A novel likely pathogenic CLCN5 variant in Dent's disease
S Hayward1,2, J Norton3, L Bownass4
1Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, UK.
BMC Nephrology
|August 28, 2023
Summary
Genetic analysis revealed a CLCN5 gene variant in four individuals with Dent's disease. This finding reclassified the variant, enabling quicker diagnosis and genetic screening for affected families.
Area of Science:
- Genetics
- Nephrology
Background:
- Dent's disease is primarily caused by pathogenic variants in the CLCN5 gene, encoding the chloride channel ClC-5.
- CLCN5 variants lead to proximal tubular dysfunction, a hallmark of Dent's disease.
Observation:
- A novel CLCN5 insertion-deletion variant (c.1744_1745delinsAA p.(Ala582Lys)) was identified in a family of three and an unrelated pediatric patient.
- Affected individuals presented with symptoms including end-stage kidney failure, proteinuria, hematuria, nephrocalcinosis, and hypercalciuria.
Findings:
- Familial segregation and identification in multiple patients confirmed the pathogenicity of the CLCN5 variant.
- The variant was reclassified from 'unknown significance' to 'likely pathogenic' based on these findings.
Implications:
- This reclassification allows for a likely diagnosis of Dent's disease without kidney biopsy for patients with this variant.
- Genetic screening can now be offered to family members of affected individuals, facilitating early detection and management.
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