title: Evidence for a founder effect for pseudoxanthoma elasticum in the Afrikaner population of South Africa.
abstract: Pseudoxanthoma elasticum (PXE) is a heritable elastic tissue disorder recently shown to be attributable to mutations in the ABCC6 ( MRP6) gene. Whereas PXE has been identified in all ethnic groups studied to date, the prevalence of this disease in various populations is uncertain, although often assumed to be similar. A notable exception however is the prevalence of PXE among South African Afrikaners. A previous report has suggested that a founder effect may explain the higher prevalence of PXE in Afrikaners, a European-derived population that first settled in South Africa in the 17th century. To investigate this hypothesis, we performed haplotype and mutational analysis of DNA from 24 South African families of Afrikaner, British and Indian descent. Among the 17 Afrikaner families studied, three common haplotypes and six different disease-causing variants were identified. Three of these mutant alleles were missense variants, two were nonsense mutations and one was a single base-pair insertion. The most common variant accounted for 53% of the PXE alleles, whereas other mutant alleles appeared at lower frequencies ranging from 3% to 12%. Haplotype analysis of the Afrikaner families showed that the three most frequent mutations were identical-by-descent, indicating a founder origin of PXE in this population.
authors.affiliation: Pacific Biomedical Research Center, University of Hawai'i, Honolulu, Hawaii, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Le Saux
authors.forename: Konstanze
authors.initials: K
authors.lastname: Beck
authors.forename: Christine
authors.initials: C
authors.lastname: Sachsinger
authors.forename: Carina
authors.initials: C
authors.lastname: Treiber
authors.forename: Harald H H
authors.initials: HH
authors.lastname: Göring
authors.forename: Katie
authors.initials: K
authors.lastname: Curry
authors.forename: Eric W
authors.initials: EW
authors.lastname: Johnson
authors.forename: Lionel
authors.initials: L
authors.lastname: Bercovitch
authors.forename: Anna-Susan
authors.initials: AS
authors.lastname: Marais
authors.forename: Sharon F
authors.initials: SF
authors.lastname: Terry
authors.forename: Denis L
authors.initials: DL
authors.lastname: Viljoen
authors.forename: Charles D
authors.initials: CD
authors.lastname: Boyd
mesh_terms: D018703:Founder Effect; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D015995:Prevalence; D011561:Pseudoxanthoma Elasticum / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D013019:South Africa / Q000453:epidemiology
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human