Kauppinen R, Peltonen L, Pihlaja H, Mustajoki P
Third Department of Medicine, University Central Hospital of Helsinki, Finland.
Hum Mutat. 1992;1(5):392-6. doi: 10.1002/humu.1380010508.
Acute intermittent porphyria (AIP) is a dominantly inherited metabolic disease caused by a partial deficiency of the third enzyme, porphobilinogen deaminase (PBGD), in the heme biosynthetic pathway. AIP has been divided into two subtypes according to the ratio of enzyme polypeptide concentration and enzyme activity measured in erythrocytes: cross-reacting immunologic material (CRIM) positive or negative. In this study six out of the seven known CRIM-positive AIP families in Finland were analyzed and two also previously identified mutations in the PBGD gene were found to be responsible for AIP in this genetically isolated population. The search for mutations was focused on exon 10 based on previously found mutations. SSCP analysis revealed a known polymorphism but the two mutations in that region were found only by direct sequencing of the PCR products. A G518-->A substitution changing Arg173 to Gln was found in three families and a C499-->T substitution changing Arg167 to Trp was detected in three families. DNA analyses of the family members revealed that conventional assays of erythrocyte PBGD activity identified correctly only 72% of the carriers for the AIP mutation.
急性间歇性卟啉病（AIP）是一种常染色体显性遗传代谢疾病，由血红素生物合成途径中第三种酶——卟胆原脱氨酶（PBGD）部分缺乏引起。根据红细胞中酶多肽浓度与酶活性的比值，AIP已被分为两种亚型：交叉反应免疫物质（CRIM）阳性或阴性。在本研究中，对芬兰7个已知的CRIM阳性AIP家族中的6个进行了分析，发现PBGD基因中两个先前已鉴定的突变在这个遗传隔离人群中导致了AIP。基于先前发现的突变，对第10外显子进行了突变搜索。单链构象多态性（SSCP）分析揭示了一个已知的多态性，但该区域的两个突变仅通过对PCR产物进行直接测序才被发现。在3个家族中发现了导致第173位精氨酸变为谷氨酰胺的G518→A替换，在3个家族中检测到导致第167位精氨酸变为色氨酸的C499→T替换。对家庭成员的DNA分析表明，传统的红细胞PBGD活性检测仅能正确识别72%的AIP突变携带者。
