caa a22 4500 397575033 CHVBK 20180308164853.0 cr unu---uuuuu 161202e199607 xx s 000 0 eng 10.1093/hmg/5.7.981 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.7.981 Identification of Three Mutations and Associated Haplotypes in the Protoporphyrinogen Oxidase Gene in South African Families with Variegate Porphyria [Elektronische Daten] [Louise Warnich, Maritha J. Kotze, Ilse M. Groenewald, Johannes Z. Groenewald, Maléne G. van Brakel, Carel J. van Heerden, J. Nico P. de Villiers, Wim J. M. van de Ven, Eric F.P.M. Schoenmakers, Shigeru Taketani, Andries E. 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 StyI restriction site, while mutation R168C would abolish a DsaI 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. © 1996 Oxford University Press Warnich Louise Department of Genetics, University of Stellenbosch, 7600 Stellenbosch, South Africa aut Kotze Maritha J. Department of Human Genetics, University of Stellenbosch, 7505 Tygerberg, South Africa aut Groenewald Ilse M. Department of Genetics, University of Stellenbosch, 7600 Stellenbosch, South Africa aut Groenewald Johannes Z. Department of Genetics, University of Stellenbosch, 7600 Stellenbosch, South Africa aut van Brakel Maléne G. Department of Genetics, University of Stellenbosch, 7600 Stellenbosch, South Africa aut van Heerden Carel J. Department of Genetics, University of Stellenbosch, 7600 Stellenbosch, South Africa aut de Villiers J. Nico P. Department of Human Genetics, University of Stellenbosch, 7505 Tygerberg, South Africa aut van de Ven Wim J. M. Laboratory for Molecular Oncology, Center for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium aut Schoenmakers Eric F.P.M. Laboratory for Molecular Oncology, Center for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium aut Taketani Shigeru Department of Hygiene, Kansai Medical University, Moriguchi, Osaka 570, Japan aut Retief Andries E. Department of Genetics, University of Stellenbosch, 7600 Stellenbosch, South Africa aut Human Molecular Genetics Oxford University Press 5/7(1996-07), 981-984 0964-6906 5:7<981 1996 5 hmg https://doi.org/10.1093/hmg/5.7.981 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.7.981 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Warnich Louise Department of Genetics, University of Stellenbosch, 7600 Stellenbosch, South Africa aut NATIONALLICENCE 700 1- Kotze Maritha J. Department of Human Genetics, University of Stellenbosch, 7505 Tygerberg, South Africa aut NATIONALLICENCE 700 1- Groenewald Ilse M. Department of Genetics, University of Stellenbosch, 7600 Stellenbosch, South Africa aut NATIONALLICENCE 700 1- Groenewald Johannes Z. Department of Genetics, University of Stellenbosch, 7600 Stellenbosch, South Africa aut NATIONALLICENCE 700 1- van Brakel Maléne G. Department of Genetics, University of Stellenbosch, 7600 Stellenbosch, South Africa aut NATIONALLICENCE 700 1- van Heerden Carel J. Department of Genetics, University of Stellenbosch, 7600 Stellenbosch, South Africa aut NATIONALLICENCE 700 1- de Villiers J. Nico P. Department of Human Genetics, University of Stellenbosch, 7505 Tygerberg, South Africa aut NATIONALLICENCE 700 1- van de Ven Wim J. M. Laboratory for Molecular Oncology, Center for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium aut NATIONALLICENCE 700 1- Schoenmakers Eric F.P.M. Laboratory for Molecular Oncology, Center for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium aut NATIONALLICENCE 700 1- Taketani Shigeru Department of Hygiene, Kansai Medical University, Moriguchi, Osaka 570, Japan aut NATIONALLICENCE 700 1- Retief Andries E. Department of Genetics, University of Stellenbosch, 7600 Stellenbosch, South Africa aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/7(1996-07), 981-984 0964-6906 5:7<981 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford