title: Nine mutations including three novel mutations among Russian patients with acute intermittent porphyria.
abstract: Acute intermittent porphyria (AIP) is a metabolic disease due to a partial deficiency of hydroxymethylbilane synthase (HMBS) in heme biosynthesis. Direct sequencing of genomic DNA samples of 11 unrelated Russian AIP patients, 32 of their relatives and 50 healthy controls from northwestern Russia including Saint Petersburg revealed nine mutations in the HMBS gene. Three novel mutations, c.825+5G>C, c.825+3_825+6del, and c.770T>C, resulted in varying amounts of abnormal transcripts, r.822_825del and [r.770U>C, r.652_771del, r.613_771del]. Six mutations, c.77G>A (p.R26H), c.517C>T (p.R173W), c.583C>T (p.R195C), c.673C>T (p.R225X), c.739T>C (p.C247R), and c.748G>C (p.E250A), have previously been identified in AIP patients from Western and other Eastern European populations. All mutations expressed in COS-1 cells demonstrated low residual activities (0.1-1%). The majority of the mutations were family-specific and also confirmed allelic heterogeneity among Russian AIP patients. The diversity of mutations may reflect the old international history of Saint Petersburg and immigration of people from other parts of Europe.
authors.affiliation: Research Program in Molecular Medicine, Biomedicum-Helsinki, University of Helsinki, Finland. vp@ppp.delfa.net
authors.forename: Elena
authors.initials: E
authors.lastname: Pischik
authors.forename: Susanna
authors.initials: S
authors.lastname: Mehtälä
authors.forename: Raili
authors.initials: R
authors.lastname: Kauppinen
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D017118:Porphyria, Acute Intermittent / Q000175:diagnosis / Q000235:genetics*; D012326:RNA Splicing / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D012426:Russia / Q000208:ethnology
chemical_list: D012333:RNA, Messenger; D011163:Hydroxymethylbilane Synthase