Molecular analysis of the CTNS gene in Jordanian families with nephropathic cystinosis

Abstract

This study is the first molecular study of infantile nephropathic cystinosis in Jordan. We successfully identified the causative CTNS mutations in Jordanian families. The results provide a basis for the early detection of the disease using molecular tools in a highly consanguineous Jordanian population.

Molecular Mechanisms and Treatment Options of Nephropathic Cystinosis

“…Remarkably, this mutation has not been observed in any studies from the Middle East or Africa. However, the c.681G>A splicing mutation, which involves the last base pair of exon nine in CTNS, is the most prevalent mutation in countries of the Middle East and is a possible founder mutation [101]. In addition, around 15% of cystinosis patients worldwide carry a nonsense mutation [102].…”

A 57 kB Genomic Deletion Causing CTNS Loss of Function Contributes to the CTNS Mutational Spectrum in the Middle East

“…c.451A>G, p.Arg151Gly, c.681G>A (p.Glu227 * ) and 0.834_842del, p. Val279_Tyr281del are the most common alleles in the Turkish population while in Egypt, c.829dup, p.Thr277Asnfs * 19 has been reported in 4 different cases. Interestingly, c.681G>A (p.Glu227 * ) is the overall most frequently identified allele detected in all Middle eastern cohorts and most variant represent stop or frameshift alleles (Table 1) (17–22, 26). Studies investigating CTNS mutations in Cystinosis patients from the Far East have likewise reported several alleles including compound heterozygous mutation c.329G>C, c.329+2T>C in Japan, c.926G>A, c.850C>T, c.18-21del/c and c.969C>G in Thailand, and compound heterozygous mutations c.329+1del andc.463_464del in China while none of the reported cases carried the 57-kb deletion (27–29) but a smaller deletion encompassing ~20 kb of genomic DNA extending from CARKL intron 1 to CTNS intron 6, c.771–793del, and a c.1515G>A variant have been reported in Tunisian nephrotic patients (30).…”