title: Acute intermittent porphyria: alternative splicing of hydroxymethylbilane synthase mRNA excludes exons 3 and 12.
abstract: The hydroxymethylbilane synthase (HMBS) mRNAs from 44 control individuals and 30 patients suffering from acute intermittent porphyria (AIP), were screened for length differences by reverse transcriptase polymerase chain reaction (RT-PCR) and any abnormalities were characterized by direct sequencing. Examination of the mRNAs extracted from the peripheral blood lymphocytes of the samples revealed varying degrees of alternative splicing, involving the removal of exons 3 and 12. Approximately 10-50% of the mRNA molecules were affected, despite the absence of genomic splice site mutations or any major deviance from consensus splice sequence values. The preliminary data obtained from this study suggest that this event is a normal occurrence in peripheral blood lymphocytes, and may not be associated with the molecular pathology responsible for AIP.
authors.affiliation: Duncan Guthrie Institute of Medical Genetics, Yorkhill, Glasgow, UK.
authors.forename: P M
authors.initials: PM
authors.lastname: Ong
authors.forename: W G
authors.initials: WG
authors.lastname: Lanyon
authors.forename: M R
authors.initials: MR
authors.lastname: Moore
authors.forename: J M
authors.initials: JM
authors.lastname: Connor
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics; D016133:Polymerase Chain Reaction; D017118:Porphyria, Acute Intermittent / Q000201:enzymology* / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D011163:Hydroxymethylbilane Synthase