Molecular analysis reveals a high mutation frequency in the first untranslated exon of the PPOX gene and largely excludes variegate porphyria in a subset of clinically affected Afrikaner families
| Autor: | Odell Loubser, J. N. P. De Villiers, Rochelle Thiart, A.E. Retief, Roberta N. Rooney, Louise Warnich, C. J. J. Oosthuizen, Maritha J. Kotze, M.M van Niekerk, Ilse M. Groenewald, Johannes Z. Groenewald |
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| Rok vydání: | 1998 |
| Předmět: |
Genetic Markers
Male Oxidoreductases Acting on CH-CH Group Donors Variegate porphyria DNA Mutational Analysis Biology Polymerase Chain Reaction White People Cohort Studies Mitochondrial Proteins Porphyrias South Africa Exon Gene Frequency Chromosome Segregation medicine Humans Point Mutation Protoporphyrinogen Oxidase Allele Mutation frequency Molecular Biology Allele frequency Netherlands Chromosomes Human Pair 14 Genetics Polymorphism Genetic Base Sequence Flavoproteins Genetic Carrier Screening Point mutation Haplotype Exons Cell Biology medicine.disease Molecular biology Pedigree Chromosomes Human Pair 1 Female Protoporphyrinogen oxidase Oxidoreductases Microsatellite Repeats |
| Zdroj: | Molecular and Cellular Probes. 12:293-300 |
| ISSN: | 0890-8508 |
| DOI: | 10.1006/mcpr.1998.0188 |
| Popis: | A subset of probands from 11 South African families with clinical and/or biochemical features of variegate porphyria (VP), but without the known protoporphyrinogen oxidase (PPOX) gene defects identified previously in the South African population, were subjected to mutation analysis. Disease-related mutation(s) could not be identified after screening virtually the entire PPOX gene by heteroduplex single-strand conformation polymorphism analysis (HEX-SSCP), although three new sequence variants were detected in exon 1 of the gene in three normal controls. The presence of these single base changes at nucleotide positions 22 (C/G), 27 (C/A) and 127 (C/A), in addition to the known exon 1 polymorphisms I-26 and I-150, indicates that this untranslated region of the PPOX gene is particularly mutation-prone. Furthermore, microsatellite markers flanking the PPOX and alpha-1 antitrypsin (PI) gene, on chromosomes 1 and 14, respectively, were used to assess the probability of involvement of these loci in disease presentation. Common alleles transmitted from affected parent to affected child were determined where possible in the mutation-negative index cases. Allelic frequencies of thesedisease-associatedalleles were compared to findings in the normal population, but no predominant disease-associated allele could be identified. Co-segregation of a specific haplotype with the disease phenotype could also not be demonstrated in a large Afrikaner family. It is concluded that further studies are warranted to determine the genetic factor(s) underlying the autosomal dominant pattern of inheritance in molecularly uncharacterized cases showing clinical symptoms of an acute porphyria. |
| Databáze: | OpenAIRE |
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