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

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.