Introduction:
Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder. It is one of the leading hereditary causes of renal Fanconi syndrome in children, with many extra-renal complications having crystal deposition in various tissues. Mutations in the CTNS gene on chromosome 17p13, which encodes the lysosomal cystine transporter cystinosin leads to the disease. The most commonly detected pathogenic mutation is the 57-kb deletion present in almost 50 % of CTNS mutant alleles of patients of North European and North American origin. We intend to report the variants seen in a cohort of Indian children with nephropathic cystinosis.
Methods:
After clinical and biochemical evaluation, Whole exome sequencing of 143 patients with renal tubular disorders, presented to two centres, one from central and other from southern India were done. We identified 11 patients with genetically confirmed Nephropathic Cystinosis.
Results:
There were 10 patients with CTNS mutation,8 males and 2 females. Median age was 5 years,(IQR: 2-7.75). The median age of onset of symptoms was 7.5 months (IQR: 7-11.5). All the patients had polyuria, polydipsia and failure to thrive. The most common variant observed was c.422C>T (p. Ser141Phe) (4/10) followed by c.807_809del (p. Ser270del) (2/10). One patient with c.759_781del (p.Gly258SerfsTer30) was found. All these variants were previously reported. One variant c.396G>A identified was not reported previously.
In two siblings with phenotypic features of cystinosis previously unreported variant was found-chr17:3560093A>G (HET); c.681+4A>G (5’ splice-site proximal) and chr17:3563233A>C (HET); c.934A>C; p. Ser312Arg, in a compound heterozygous state. On segregation analysis, one allele was found in mother and other in Father.
Conclusions:
The mutation spectrum in Indian children was different from the previously reported 57 kb deletion in North American and North European origin. None of them had the Classical 57 Kb Deletion. Variants previously not reported were identified in 3 patients, with phenotypic features of Nephropathic cystinosis.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.