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CRIM‐positive mutations of acute intermittent porphyria in Finland
Author(s) -
Kauppinen R.,
Peltonen L.,
Pihlaja H.,
Mustajoki P.
Publication year - 1992
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.1380010508
Subject(s) - acute intermittent porphyria , porphobilinogen deaminase , biology , genetics , porphobilinogen , single strand conformation polymorphism , mutation , exon , microbiology and biotechnology , gene , enzyme , porphyria , point mutation , biochemistry , endocrinology
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 G 518 → A substitution changing Arg 173 to Gln was found in three families and a C 499 → T substitution changing Arg 167 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. © 1992 Wiley‐Liss, Inc.