Clinical, biochemical, and molecular spectrum of nephropathic cystinosis: Two novel CTNS mutations

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BACKGROUND: Nephropathic cystinosis (NC) is an autosomal recessive disease. Mutations in the CTNS gene encoding the lysosomal membrane cystine transporter cystinosin are identified as the molecular basis of cystinosis. AIM: To evaluate the clinical phenotype, biochemical profile, and screen for mutations in CTNS genes in NC patients. METHODS: Thirteen patients from 11 unrelated families were clinically suspected, for whom biochemical evaluation and screening of pathogenic CTNS gene mutations were performed. RESULTS: Polymorphonuclear leukocyte cells leucocytes cystine assay range 4-13 nmol ½ cystine/mg proteins and median 5.5 nmol ½ cystine/mg proteins at follow up. Eight patients (66.6%) had high activity of chitotriosidase (101-417 umol/l/h, median 139.5), compared with normal subjects (4-80 nmol/l/h, mean 23 nmol/l/h). Value range was reduced to (56-175 umol/l/h, median 89) on treatment. Furthermore, two patients had high thyroid stimulating hormone level (36.1, 79. UI/ml), that normalized to (8.5, 6.4 UI/ml) during follow up. Nine pathogenic variants were identified in thirteen patients; two novel variants in two separate families, P111Rfs*7 and K335R, in exons 7 and 12, respectively, and seven known pathogenic variants. CONCLUSION: Our study highlights the importance of close follow up of NC patients and expands the mutational spectrum of CTNS gene, as two novel mutations are identified in two unrelated families.

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