Mutational Spectrum of the CTNS Gene in Egyptian Patients with Nephropathic Cystinosis

Abstract

Background: Nephropathic cystinosis is a rare autosomal recessive disorder caused by mutations in the CTNS gene, encoding for cystinosin, a carrier protein transporting cystine out of lysosomes. Its deficiency leads to cystine accumulation and cell damage in multiple organs, especially in the kidney. In this study, we aimed to provide the first report describing the mutational spectrum of Egyptian patients with nephropathic cystinosis and their genotype-phenotype correlation.Methods: Fifteen Egyptian patients from 13 unrelated families with infantile nephropathic cystinosis were evaluated clinically, biochemically, and genetically. Screening for the common 57-kb deletion was performed by standard multiplex PCR, followed by direct sequencing of the ten coding exons, exon-intron interfaces, and promoter region.

The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis

“…Shahkarami et al (18) studied patients with cystinosis in Iran, and they showed that none of their patients had the 57-kb deletion and that the most common mutation was c.681G.A (p.E227E; 40%). Soliman et al (19) studied patients with cystinosis in Egypt and identified c.681G.A (p.E227E) in 7.7% of the patients. The high frequency of c.681G.A (p.E227E) in this region of the world is indicative of a possible founder mutation.…”

The renal Fanconi syndrome in cystinosis: pathogenic insights and therapeutic perspectives

“…Another founder mutation, involving a 57 kb deletion in CTNS , is the most common cause of cystinosis, affecting 65% of patients of northern European descent 13,27,57 but almost never occurs in other families 58–61 . Cystinosis is also reported in countries with high levels of consanguinity such as some countries in the Middle East, but accurate prevalence data are lacking 58,61–64 . The low reported frequency of cystinosis in Russia 65 , India 66 and China 67 likely reflects underdiagnosis.…”

Molecular Basis of Cystinosis: Geographic Distribution, Functional Consequences of Mutations in the <b><i>CTNS</i></b> Gene, and Potential for Repair

“…Still, large geographic regions, such as sub-Saharan Africa, South-East Asia and the Far East are underrepresented in the genetic spectrum of their cystinosis patients. Although accurate statistics are lacking in the developing world [21], recent studies from the Middle East [17][18][19][20], Mexico [22] and South Africa [23] may indicate that the incidence of cystinosis in many of these countries is expected to be higher than that of Europe and North America. Moreover, many cystinosis patients in poor countries remain undiagnosed and die at a young age due to complications of the disease [24].…”

“…Notably over the last decade, an increasing number of reports have been published on CTNS gene mutations in some of the developing nations' populations [17][18][19][20]. Still, large geographic regions, such as sub-Saharan Africa, South-East Asia and the Far East are underrepresented in the genetic spectrum of their cystinosis patients.…”

“…This deletion represents over 50% of mutant alleles in cystinosis patients of Northern European ancestry; however, it is completely absent in all reported patients from the Middle East, Asia and Africa [16], suggesting a founder mutation. Other important founder mutations can be encountered in certain populations or certain geographic loci, such as the c.1015G>A in the Amish population in Western Ontario, Canada [26], the c.971-12G>A in the black population of South Africa [23] and the c.681G>A in the Middle East [17][18][19]. A more detailed description of the genetic map of cystinosis is needed to elucidate the similarities and the differences between patients all over the world and to prepare for individualized disease treatment targeting gene repair.…”