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

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. Cystinosis: New mutations underlying a kidney disorder Researchers have identified new mutations involved in cystinosis, a genetic disorder which is a common cause of kidney disease in children. The most common and severe form, infantile nephropathic cystinosis, causes growth retardation and kidney defects in infants, with kidney failure usually occuring before the child is ten. As the second study of cystinosis in the Iranian population, Majid Fardaei ’s team at the Shiraz University of Medical Sciences, Iran, sequenced the CTNS gene in 20 Iranian patients with infantile nephropathic cystinosis. They found seven different mutations in the patients, including the most common mutation in Middle Eastern populations, and previously unidentified mutations. The team also identified a genetic marker associated with the mutations which may be useful in screening for carriers, although the marker will first need to be studied in a larger sample.