[Molecular genetic study of acute intermittent porphyria in Russia: mutation analysis and functional polymorphism search in porphobilinogen deaminase gene].

Abstract	Acute intermittent porphyria (AIP) is an autosomal dominant hereditary disease, caused by partial deficiency of porphobilinogen deaminase (PBGD), one of the key enzymes ofheme biosynthesis. This study describes molecular genetics of AIP in Russia. Mutation analysis of PBGD gene in 70 unrelated patients revealed 47 various genetic defects, 28 of which had not been described previously. Mutations 53delT and Argl 73 Trp (recorded 8 times, in total 23%) proved to be the most common in Russia. Microdeletion 53delThas monophyletic origin and was found only in Russia. Molecular genetic examination of 132 relatives of AIP patients from 40 families revealed 52 latent carriers of the disease. Low (about 10%) AIP penetrance indicates that a mutation in the PBGD gene is an important but not sufficient prerequisite for clinical manifestation of the disease. Modulation of penetrance in erythropoietic protoporphyria by coinheritance of a mutant allele and a functionally defective wild type allele of ferrochetalase gene has been shown previously. We hypothesized that similar mechanism works in AIP. Sequencing of the full length PBGD genes from unrelated AIP patients as well as SN P analysis, and the analysis of abnormal PBGD mRNA splicing showed that in case ofAIP, this hypothesis is not true and some other factors are responsible for the penetrance of this disease.
Authors	V L Surin, Iu A Luchinina, D S Selivanova, Ia S Pustovoĭt, I S Karpova, A V Pivnik, A V Luk'ianenko, S K Kravchenko
Journal	Genetika (Genetika) Vol. 46 Issue 4 Pg. 540-52 (Apr 2010) ISSN: 0016-6758 [Print] Russia (Federation)
PMID	20536026 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Hydroxymethylbilane Synthase Ferrochelatase
Topics	Alleles Alternative Splicing (genetics) DNA Mutational Analysis (methods) Female Ferrochelatase (genetics, metabolism) Humans Hydroxymethylbilane Synthase (genetics) Male Mutation Penetrance Polymorphism, Single Nucleotide Porphyria, Acute Intermittent (enzymology, genetics) Russia

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