Experimental Nephrology and Genetics: Research Article

Mollataheri A.a· Mojbafan M.a,b· Hosseini R.c· Houman N.c,d· Mousavi M.b· Otoukesh H.c

Author affiliations

aDepartment of Medical Genetics, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
bDepartment of Medical Genetics, Ali-Asghar Children’s Hospital, Tehran, Iran
cDepartment of Pediatric Nephrology, Ali-Asghar Children’s Hospital, Tehran, Iran
dClinical Research Development Center, Iran University of Medical Sciences, Tehran, Iran

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Article / Publication Details

First-Page Preview

Received: June 21, 2022
Accepted: November 21, 2022
Published online: January 16, 2023

Number of Print Pages: 8
Number of Figures: 2
Number of Tables: 2

ISSN: 1660-8151 (Print)
eISSN: 2235-3186 (Online)

For additional information: https://www.karger.com/NEF

Abstract

Introduction: Dent’s disease is an X-linked inherited renal tubular disorder characterized by proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, rickets, and end-stage renal disease. Almost 60% of patients have causative mutations in the CLCN5 gene (Dent 1), and 15% of affected individuals have mutations in the OCRL1 gene (Dent 2). The aims of this study are to identify CLCN5 mutations in Iranian families with Dent’s disease and to characterize the associated clinical syndromes. Methods: We studied 14 patients from 13 unrelated Iranian families with a clinical diagnosis of Dent’s disease. Proteinuria was detected in all patients. Nephrolithiasis was found in 5 patient, and hematuria in 2 patients. Most of the affected individuals had nephrocalcinosis. PCR-sequencing for the CLCN5 gene was performed in all 14 patients. Next-generation sequencing (NGS) has also been performed in one patient who we did not find causative mutation. Results: We identified four different CLCN5 mutations including one missense mutation (c.731C>T), one nonsense mutation (c.100C>T), and two novel mutations, consisting of one frameshift mutation (c.1241_1242dupAA) and one splicing mutation (c.805-2A>G). We also identified one OCRL1 mutation, one splicing mutation (c.1466 + 1G>A), using NGS. Conclusion: This is the first report to characterize mutations in the CLCN5 gene in Iranian patients with Dent’s disease and expands the spectrum of CLCN5 mutations by reporting two novel mutations, c.1241_1242dupAA and c.805-2A>G.

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First-Page Preview

Received: June 21, 2022
Accepted: November 21, 2022
Published online: January 16, 2023

Number of Print Pages: 8
Number of Figures: 2
Number of Tables: 2

ISSN: 1660-8151 (Print)
eISSN: 2235-3186 (Online)

For additional information: https://www.karger.com/NEF

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