title: Spectrum of genetic variation at the ABCC6 locus in South Africans: Pseudoxanthoma elasticum patients and healthy individuals.
abstract: BACKGROUND
  Pseudoxanthoma elasticum (PXE) is an autosomal recessive metabolic disorder with ectopic mineralization in the skin, eyes and cardiovascular system. PXE is caused by mutations in ABCC6.
  
  
  OBJECTIVE
  To examine 54 unrelated South African PXE patients for ABCC6 PXE causing mutations.
  
  
  METHODS
  Patients were screened for mutations in ABCC6 using two strategies. The first involved a comprehensive screening of all the ABCC6 exons and flanking regions by dHPLC or sequencing whereas the second involved screening patients only for the common PXE mutations. The ABCC6 gene was screened in ten white and ten black healthy unrelated South Africans in order to examine the level of common non-PXE associated variation.
  
  
  RESULTS
  The Afrikaner founder mutation, R1339C, was present in 0.41 of white ABCC6 PXE alleles, confirming the founder effect and its presence in both Afrikaans- (34/63 PXE alleles) and English-speakers (4/28). Eleven mutations were detected in the white patients (of European origin), including two nonsense mutations, 6 missense mutations, two frameshift mutations and a large deletion mutation. The five "Coloured" patients (of mixed Khoisan, Malay, European and African origin) included three compound heterozygotes with R1339C as one of the mutations. The three black patients (sub-Saharan African origin) were all apparent homozygotes for the R1314W mutation. Blacks showed a trend towards a higher degree of neurtral variation (18 variants) when compared to whites (12 variants).
  
  
  CONCLUSIONS
  Delineation of the ABCC6 mutation profile in South African PXE patients will be used as a guide for molecular genetic testing in a clinical setting and for genetic counselling.
authors.affiliation: Division of Human Genetics, National Health Laboratory Service and School of Pathology, University of the Witwatersrand, Johannesburg, South Africa. michele.ramsay@nhls.ac.za
authors.forename: Michèle
authors.initials: M
authors.lastname: Ramsay
authors.forename: Tarryn
authors.initials: T
authors.lastname: Greenberg
authors.forename: Zane
authors.initials: Z
authors.lastname: Lombard
authors.forename: Robyn
authors.initials: R
authors.lastname: Labrum
authors.forename: Steven
authors.initials: S
authors.lastname: Lubbe
authors.forename: Shaun
authors.initials: S
authors.lastname: Aron
authors.forename: Anna-Susan
authors.initials: AS
authors.lastname: Marais
authors.forename: Sharon
authors.initials: S
authors.lastname: Terry
authors.forename: Lionel
authors.initials: L
authors.lastname: Bercovitch
authors.forename: Denis
authors.initials: D
authors.lastname: Viljoen