Browsing by Author "Koegelenberg, Adriaan Jacobus"
Now showing 1 - 1 of 1
Results Per Page
Sort Options
- ItemMolecular epidemiological study of variegate porphyria (VP) to determine the frequency of the founder gene mutation in South Africa(Stellenbosch : Stellenbosch University, 2003-03) Koegelenberg, Adriaan Jacobus; Warnich, L.; Stellenbosch University. Faculty of AgriScience. Dept. of Genetics.ENGLISH ABSTRACT: Variegate porphyria (VP; OMIM 176200) is caused by mutations in the protoporphyrinogen oxidase gene (PPOX) and is inherited as an autosomal dominant trait, displaying incomplete penetrance. Manifestation of VP includes photosensitivity and potentially fatal acute porphyric attacks. The incidence of VP in South Africa is the highest in the world due to a founder effect. In 1960 Geoffrey Dean estimated the frequency of VP to be 0.3% in the Caucasian South African population. However, this estimate is questionable on the grounds of genealogical and biochemical methods used, and as indicated by more recent records from diagnostic laboratories reported here. The aim of this study was to determine the frequency of the VP founder mutation (R59W) within two South African populations (Caucasian and mixed ancestry) by means of a highly specific DNA test. Various methods of blood sample collection, DNA isolation and R59W mutation detection, suitable for a large-scale population-screening study, were evaluated. Blood samples were obtained from 4 072 participants at blood transfusion clinics, pathology clinics and maternity wards from three provinces within South Africa. Blood sample collection on FTA cards (Whatman BioScience) with subsequent DNA isolation and SSCP analysis were found to be the most appropriate methods. Four of the participants tested were positive for the R59W mutation. All four were from the 3 233 Caucasian individuals tested while three of these were Afrikaansspeaking, confirming the high prevalence of the founder mutation in the South African Afrikaans-speaking Caucasian population (Afrikaner), as previously reported. One of the two adult R59W positive participants was unaware of her carrier status, in accordance with incomplete penetrance of the trait recently estimated as 60%. The mother of one of the newborn babies found to be R59W positive was also not aware of VP in the family, indicating that ignorance regarding VP status in South Africa is a matter of some concern. The estimated frequency of 0.12% (4 / 3 233) for the R59W mutation is significantly lower than the frequency of 0.3% estimated previously, and analysis of the different populations sampled yielded interesting results. Only one of 2 093 (0.05%) participants in the Caucasian blood transfusion sample was mutationpositive. It is possible that the sample from this group was not unbiased, as porphyries were discouraged to donate blood in the past. One of 761 (0.13%) Caucasian participants from pathology clinics was mutation-positive. This sample was probably not unbiased either, since suspected porphyries are referred to these clinics by physicians. Two of 379 (0.53%) Caucasian newborn individuals tested positive, yielding a much higher frequency than the previous estimate by Dean. Although the sample size was very small, it was probably unbiased and therefore provides the best estimate. It is suggested that the sample size of this group be increased in order to improve the accuracy of the founder mutation frequency estimation in South Africa and to determine whether the issue of underdiagnosis and the resulting risk of potentially fatal acute attacks should be addressed by appropriate genetic testing in the future.