Department of Dermatology Euregional Porphyria Center Maastricht GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, the Netherlands.
Br J Dermatol. 2012 Feb;166(2):261-5. doi: 10.1111/j.1365-2133.2011.10606.x.
Variegate porphyria (VP) is due to a partial deficiency of protoporphyrinogen oxidase (PPOX), the seventh enzyme in the haem biosynthetic pathway. Clinically, VP is characterized by photosensitivity and acute neurovisceral attacks that can manifest separately or together in affected individuals. The disease is inherited in an autosomal dominant fashion with incomplete penetrance and PPOX gene mutations associated with VP are usually unique to patients and their families. In South Africa, however, VP is highly prevalent as the result of a founder mutation, designated p.R59W. Previous genealogical and haplotype studies showed a link between South African and Dutch carriers of p.R59W and it was suggested that this mutation was introduced to South Africa by Dutch settlers at the end of the 17th century.
To perform extended haplotype analysis in six South African and Dutch VP families with the p.R59W mutation.
Haplotyping of 13 microsatellite markers flanking the PPOX gene on chromosome 1q22-23 and five informative single nucleotide polymorphisms within and around the gene.
A core haplotype cosegregated in all families studied.
Our data deliver further confirmation that the South African and Dutch VP families carrying mutation p.R59W shared a common ancestor.
杂色卟啉症（VP）是由于原卟啉原氧化酶（PPOX）部分缺乏引起的，PPOX 是血红素生物合成途径中的第七种酶。临床上，VP 的特征是光敏性和急性神经内脏发作，在受影响的个体中可以单独或同时表现出来。该疾病以常染色体显性遗传方式遗传，具有不完全外显率，与 VP 相关的 PPOX 基因突变通常是患者及其家族所特有的。然而，在南非，由于一个称为 p.R59W 的创始人突变，VP 的发病率非常高。先前的系谱和单倍型研究表明，南非和荷兰的 p.R59W 携带者之间存在联系，并表明该突变是 17 世纪末荷兰定居者引入南非的。
对六个携带 p.R59W 突变的南非和荷兰 VP 家族进行扩展单倍型分析。
对 13 个位于 1q22-23 染色体上 PPOX 基因侧翼的微卫星标记和基因内及周围的 5 个信息单核苷酸多态性进行单倍型分析。
所有研究的家族中都存在核心单倍型共分离。
我们的数据进一步证实，携带突变 p.R59W 的南非和荷兰 VP 家族具有共同的祖先。
