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

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.

To evaluate the clinical phenotype, biochemical profile, and screen for mutations in CTNS genes in NC patients.

Thirteen patients from 11 unrelated families were clinically suspected, for whom biochemical evaluation and screening of pathogenic CTNS gene mutations were performed.

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.

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.