Spectrum of genetic variation at the ABCC6 locus in South Africans: Pseudoxanthoma elasticum patients and healthy individuals.
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.
Ramsay
Michèle
M
Division of Human Genetics, National Health Laboratory Service and School of Pathology, University of the Witwatersrand, Johannesburg, South Africa. michele.ramsay@nhls.ac.za
Greenberg
Tarryn
T
Lombard
Zane
Z
Labrum
Robyn
R
Lubbe
Steven
S
Aron
Shaun
S
Marais
Anna-Susan
AS
Terry
Sharon
S
Bercovitch
Lionel
L
Viljoen
Denis
D