Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Clinical and Chemical Pathology

Background: Nephropathic cystinosis is an autosomal recessive metabolic, lifelong disease characterized by lysosomal cystine accumulation throughout the body that commonly presents in infancy with a renal Fanconi syndrome and, if untreated, leads to end-stage kidney disease (ESKD) in the later childhood. The molecular basis is due to mutations in lysosomal cystine transporter Gene, CTNS gene, which encoding for the lysosomal cystine-proton cotransporter, cystinosin. During adolescence and adulthood, extrarenal manifestations of cystinosis develop and require multidisciplinary care. Despite substantial improvement in prognosis due to cystine-depleting therapy with cysteamine, no cure of the disease is currently available. Aim of the work: Mutation scanning of the coding exons of CTNS gene (exon 3 to exon 12). Subjects and methods: CTNS gene was scanned for mutations in 24 Nephropathic Cystinosis patients using High resolution melting analysis (by Real-Time PCR) followed by mutation confirmation using sanger sequencing. Results: CTNS gene mutations were detected in 17 out of 24 nephropathic cystinosis patients (71%). Exon 10 was the most frequent exon harbouring mutations. 13 patients (54.2%) had mutations in exon 10: c.809_811delCCT small deletion (33.3%), c.828_829insA 16.7% and c.734G>A 4.2%

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