纯合性变异性卟啉症：20年随访及分子缺陷特征分析

Homozygous variegate porphyria: 20 y follow-up and characterization of molecular defect.

作者信息

Kauppinen R, Timonen K, von und zu Fraunberg M, Laitinen E, Ahola H, Tenhunen R, Taketani S, Mustajoki P

机构信息

Department of Medicine, Division of Diabetology, Dermatology and Clinical Chemistry of the University of Helsinki, Finland.

出版信息

J Invest Dermatol. 2001 Apr;116(4):610-3. doi: 10.1046/j.1523-1747.2001.01293.x.

DOI:10.1046/j.1523-1747.2001.01293.x

PMID:11286631

Abstract

The long-term follow-up of a homozygous variegate porphyria patient revealed severe photosensitivity accompanied by mild sensory neuropathy and IgA nephropathy. A 35T to C transition in exon 2 (I12T) and a 767C to G transversion in exon 7 (P256R) of the protoporphyrinogen oxidase gene were identified from both alleles of the patient's cDNA and genomic DNA samples. Both prokaryotic and eukaryotic expression studies showed that the first mutation in the evolutionary conserved region resulted in a decrease in the protoporphyrinogen oxidase activity in contrast to the polymorphic substitution in exon 7, which affected the function of the enzyme assayed in Escherichia coli but not COS-1 cells.

摘要

对一名纯合性杂色卟啉症患者的长期随访显示，患者存在严重的光敏反应，并伴有轻度感觉神经病变和IgA肾病。从患者的cDNA和基因组DNA样本的两个等位基因中，均鉴定出原卟啉原氧化酶基因外显子2（I12T）的35T到C转换以及外显子7（P256R）的767C到G颠换。原核和真核表达研究均表明，进化保守区域的第一个突变导致原卟啉原氧化酶活性降低，而外显子7中的多态性替代则不同，它影响了在大肠杆菌中检测到的酶功能，但对COS-1细胞中的酶功能没有影响。