Molecular analysis of cystinosis: probable Irish origin of the most common French Canadian mutation

Eur J Hum Genet. 1999 Sep;7(6):671-8. doi: 10.1038/sj.ejhg.5200349.


Infantile nephropathic cystinosis, an autosomal recessive disease characterized by a lysosomal accumulation of cystine, presents as failure to thrive, rickets and proximal renal tubular acidosis. The cystinosis gene, CTNS, which maps to chromosome 17p13, encodes a predicted 55 kDa protein with characteristics of a lysosomal membrane protein. We have conducted extensive linkage analysis in a French Canadian cystinosis cohort identifying a founding haplotype present in approximately half (21/40) of the chromosomes studied. Subsequent mutational analysis, in addition to identifying two novel mutations, has unexpectedly revealed a mutation which has been previously found in Irish (but not French) cystinotic families on these 21 French Canadian chromosomes. Haplotype analysis of two Irish families with this mutation supports the hypothesis that Celtic chromosomes represent an extensive portion of cystinosis chromosomes in French Canada. Our analysis underlines the genetic heterogeneity of the French Canadian population, reflecting a frequently unrecognized contribution from non-Gallic sources including the Irish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems, Neutral
  • Canada / ethnology
  • Chromosomes, Human, Pair 7
  • Cystinosis / ethnology
  • Cystinosis / genetics*
  • DNA Mutational Analysis
  • Exons
  • Female
  • Founder Effect
  • Gene Deletion
  • Genetic Markers
  • Glycoproteins*
  • Haplotypes
  • Humans
  • Ireland / ethnology
  • Male
  • Membrane Proteins / genetics*
  • Membrane Transport Proteins
  • Models, Genetic
  • Mutation*
  • Pedigree
  • Point Mutation
  • Polymorphism, Single-Stranded Conformational


  • Amino Acid Transport Systems, Neutral
  • CTNS protein, human
  • Genetic Markers
  • Glycoproteins
  • Membrane Proteins
  • Membrane Transport Proteins