title: Mutation spectrum and founder chromosomes for the ABCA4 gene in South African patients with Stargardt disease.
abstract: OBJECTIVE
  To assess the mutation spectrum of ABCA4 underlying Stargardt disease (STGD) in South Africa (SA) and to determine whether there is a single or a few founder chromosomes in SA STGD families.
  
  
  METHODS
  Sixty-four probands exhibiting the STGD phenotype were screened for mutations in the 50 exons of ABCA4 by single-strand conformational polymorphism-heteroduplex analysis sequencing and restriction fragment length polymorphism analysis. Microsatellite marker haplotyping was used to determine the ancestry in 10 families.
  
  
  RESULTS
  Fifty-seven ABCA4 disease-associated alleles were identified that comprised 16 different sequence variants, of which two were novel, in 40 individuals of the cohort of 64 subjects. The most common variants identified included the C1490Y, L2027F, R602W, V256splice, R152X, and 2588G-->C mutations. The C1490Y variant was the most common disease-associated variant identified (19/64 subjects) and was absent in 392 control chromosomes. At least 10 ABCA4 disease-associated haplotypes were identified. Two of these haplotypes, which carried the C1490Y mutation, were identified in three unrelated families.
  
  
  CONCLUSIONS
  Results suggest that ABCA4 is the major gene underlying STGD in the cohort investigated. Five of the six common sequence variants identified were at a higher frequency in the SA cohort than reported in published data on individuals of similar ancestry. The mutation and haplotype data suggests that there are several ancestral haplotypes underlying STGD in SA. There seems to be at least two different origins for the common C1490Y mutation, as well as two for the R602W mutation, thereby suggesting several founder effects for STGD in SA.
authors.affiliation: Division of Human Genetics, University of Cape Town, Observatory, Cape Town, South Africa.
authors.forename: Alison V
authors.initials: AV
authors.lastname: September
authors.forename: Anna A
authors.initials: AA
authors.lastname: Vorster
authors.forename: Rajkumar S
authors.initials: RS
authors.lastname: Ramesar
authors.forename: L Jacquie
authors.initials: LJ
authors.lastname: Greenberg
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002877:Chromosomes, Human / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D018703:Founder Effect; D006239:Haplotypes; D020180:Heteroduplex Analysis; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D013019:South Africa
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters