Common mutation causes cystinosis in the majority of black South African patients

Pediatr Nephrol. 2015 Apr;30(4):595-601. doi: 10.1007/s00467-014-2980-7. Epub 2014 Oct 18.

Abstract

Background: The mutations responsible for cystinosis in South African patients are currently unknown. A pertinent question is whether they are similar to those described elsewhere in the world.

Methods: Children who were being managed for cystinosis in the Western Cape Province of South Africa between 2002 and 2013 were studied. All underwent molecular analysis to detect sequence variations in the cystinosis gene.

Results: This cohort study included 20 patients, 13 of whom were Xhosa-speaking black South Africans and seven were Cape Coloureds (mixed race); none were Caucasian. All had nephropathic infantile-type cystinosis with evidence of proximal tubulopathy, with glycosuria and renal phosphate wasting. Diagnosis was confirmed in 19 cases by demonstrating an elevated cystine concentration in leukocytes. Molecular analysis of the cystinosin gene revealed that 19 patients had a G > A mutation in intron 11 (CTNS-c.971-12G > A p.D324AfsX44) which caused an out-of-frame 10-bp insertion. Of these 19 patients, 16 were homozygous for this mutation, which was the most frequent mutation identified in the alleles of the black South African and Cape Coloured patients (96 and 71 %, respectively).

Conclusion: We recommend that black South African and Cape Coloured patients presenting with cystinosis be tested for CTNS-c.971-12G > A in the first instance, with the possibility of prenatal testing being offered to at-risk families.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amino Acid Transport Systems, Neutral / genetics*
  • Black People / genetics*
  • Child
  • Child, Preschool
  • Cystine / blood
  • Cystinosis / genetics*
  • Female
  • Humans
  • Infant
  • Male
  • Point Mutation / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • RNA, Messenger / genetics
  • Retrospective Studies
  • South Africa / epidemiology

Substances

  • Amino Acid Transport Systems, Neutral
  • CTNS protein, human
  • RNA, Messenger
  • Cystine