Human Molecular Genetics, Vol 5, 981-984, Copyright © 1996 by Oxford University Press
L Warnich, MJ Kotze, IM Groenewald, JZ Groenewald, MG van Brakel, CJ van Heerden, JN de Villiers, WJ van de Ven, EF Schoenmakers, S Taketani and AE Retief
Mutation analysis of genomic DNA samples obtained from 17 unrelated South
African patients with variegate porphyria (VP) revealed three novel
missense mutations in the protoporphyrinogen oxidase (PPOX) gene. A common
C to T transition at nucleotide position 452 (R59W) was identified in 15 of
the patients analysed, while base changes at positions 336 (H20P) and 779
(R168C) were identified in the remaining two patients. Using protein
analysis software we were able to predict that all three mutations have a
similar biophysical effect on the protein, being the disturbance of
amphiphatic regions within the protein, which might result in misfolding of
the protein. Mutation R59W, identified in the majority of South African VP
families, was shown to create a Styl restriction site, while mutation R168C
would abolish a Dsal restriction site in genomic DNA of affected
individuals. As 100% of the index patients analysed were molecularly
characterized, the combined use of restriction enzyme and single-strand
conformation polymorphism (SSCP) analysis now allows a rapid and accurate
diagnosis of VP in South Africa. Mutation R59W was furthermore shown to be
in association with one of four potential haplotypes defined by two newly
described polymorphisms in exon 1 of the PPOX gene. Our molecular data thus
strongly support the founder hypothesis for VP in South Africa.
ARTICLES
Identification of three mutations and associated haplotypes in the protoporphyrinogen oxidase gene in South African families with variegate porphyria
Department of Genetics, University of Stellenbosch, South Africa.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. R. Corradi, A. V. Corrigall, E. Boix, C. G. Mohan, E. D. Sturrock, P. N. Meissner, and K. R. Acharya Crystal Structure of Protoporphyrinogen Oxidase from Myxococcus xanthus and Its Complex with the Inhibitor Acifluorfen J. Biol. Chem., December 15, 2006; 281(50): 38625 - 38633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. September, A. A. Vorster, R. S. Ramesar, and L. J. Greenberg Mutation Spectrum and Founder Chromosomes for the ABCA4 Gene in South African Patients with Stargardt Disease Invest. Ophthalmol. Vis. Sci., June 1, 2004; 45(6): 1705 - 1711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Hift, B. P. Davidson, C. van der Hooft, D. M. Meissner, and P. N. Meissner Plasma Fluorescence Scanning and Fecal Porphyrin Analysis for the Diagnosis of Variegate Porphyria: Precise Determination of Sensitivity and Specificity with Detection of Protoporphyrinogen Oxidase Mutations as a Reference Standard Clin. Chem., May 1, 2004; 50(5): 915 - 923. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. von und zu Fraunberg, T. Nyronen, and R. Kauppinen Mitochondrial Targeting of Normal and Mutant Protoporphyrinogen Oxidase J. Biol. Chem., April 4, 2003; 278(15): 13376 - 13381. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Hall, E. M. Wijsman, J. L. Roos, J. A. Gogos, and M. Karayiorgou Extended Intermarker Linkage Disequilibrium in the Afrikaners Genome Res., June 1, 2002; 12(6): 956 - 961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Donnelly, S. Detombe, and J. T. Hindmarsh Single-Strand Conformational Polymorphism and Denaturing Gradient Gel Electrophoresis in Screening for Variegate Porphyria: Identification of Two New Mutations Ann. Clin. Lab. Sci., April 1, 2002; 32(2): 107 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Kidd, R M Peek, A J Lastovica, D A Israel, A F Kummer, and J A Louw Analysis of iceA genotypes in South African Helicobacter pylori strains and relationship to clinically significant disease Gut, November 1, 2001; 49(5): 629 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Kidd, A J Lastovica, J C Atherton, and J A Louw Conservation of the cag pathogenicity island is associated with vacA alleles and gastroduodenal disease in South African Helicobacter pylori isolates Gut, July 1, 2001; 49(1): 11 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Christiansen, A. Bygum, M. Kaehne, A. Jensen, M. Horder, and N. E. Petersen Mutation Screening of the Entire Coding Region of the Protoporphyrinogen Oxidase Gene Using Denaturing Gradient Gel Electrophoresis and Denaturing HPLC Clin. Chem., June 1, 2001; 47(6): 1115 - 1117. [Full Text] [PDF]
|
|
|
|
 |
|
 M. O. Doss, A. Kuhnel, and U. Gross ALCOHOL AND PORPHYRIN METABOLISM Alcohol Alcohol., March 1, 2000; 35(2): 109 - 125. [Abstract] [Full Text] [PDF]
|
|