Mutation analysis of the CTNS gene in Iranian patients with infantile nephropathic cystinosis: identification of two novel mutations

Majid Fardaei,Mitra Basiratnia,Forough Sadeghipour,Ali Derakhshan

doi:10.1038/hgv.2017.38

Abstract

Nephropathic cystinosis is an inherited lysosomal transport disorder caused by mutations in the CTNS gene that encodes for a lysosomal membrane transporter, cystinosin. Dysfunction in this protein leads to cystine accumulation in the cells of different organs. The accumulation of cystine in the kidneys becomes apparent with renal tubular Fanconi syndrome between 6 and 12 months of age and leads to renal failure in the first decade of life. The aim of this study was to analyze the CTNS mutations in 20 Iranian patients, from 20 unrelated families, all of whom were afflicted with infantile nephropathic cystinosis. In these patients, seven different mutant alleles were found, including two new mutations, c.517T>C; p.Y173H and c.492_515del, that have not been previously reported. In addition, we observed that c.681G>A, the common Middle Eastern mutation, was the most common mutation in our patients. Moreover, a new minisatellite or variable number of tandem repeat marker (KX499495) was identified at the CTNS gene. Seven different alleles were found for this marker, and its allele frequency and heterozygosity degree were calculated in cystinosis patients and healthy individuals.

Highlights

Fanconi syndrome, is a lysosomal transport disorder with an autosomal recessive inheritance pattern, resulting from different mutations in the CTNS gene that is located on chromosome 17p13.1,2 The CTNS gene contains 12 exons with a coding region of 1,104 bp.[3]
The last 10 exons encode a lysosomal transmembrane protein with 367 amino acids called cystinosin. This protein consists of seven putative transmembrane domains (TM) and two lysosomal targeting motifs.[4,5]
Twenty unrelated Iranian patients, 15 males and 5 females, with infantile nephropathic cystinosis were included in this study

Summary

INTRODUCTION

Fanconi syndrome, is a lysosomal transport disorder with an autosomal recessive inheritance pattern, resulting from different mutations in the CTNS gene that is located on chromosome 17p13.1,2 The CTNS gene contains 12 exons with a coding region of 1,104 bp.[3] The last 10 exons encode a lysosomal transmembrane protein with 367 amino acids called cystinosin. This protein consists of seven putative transmembrane domains (TM) and two lysosomal targeting motifs.[4,5] Cystinosin dysfunction leads to deficient cystine transport and accumulation in cells of different organs, in the kidney, cornea and thyroid.[3]. We determined the allele frequency of the newly identified minisatellite marker at the CTNS gene in cystinosis patients and healthy individuals

MATERIALS AND METHODS

Findings

RESULTS