title: Tafazzin splice variants and mutations in Barth syndrome.
abstract: Barth syndrome is caused by mutations in the TAZ (tafazzin) gene on human chromosome Xq28. The human tafazzin gene produces four major mRNA splice variants; two of which have been shown to be functional (TAZ lacking exon 5 and full-length) in complementation studies with yeast and Drosophila. This study characterizes the multiple alternative splice variants of TAZ mRNA and their proportions in blood samples from a cohort of individuals with Barth syndrome (BTHS). Because it has been reported that collection and processing methods can affect the expression of various genes, we tested and chose a stabilizing medium for collecting, shipping and processing of the blood samples of these individuals. In both healthy controls and in BTHS individuals, we found a greater variety of alternatively spliced forms than previously described, with a sizeable proportion of minor splice variants besides the four dominant isoforms. Individuals with certain exonic and intronic splice mutations produce additional mutant mRNAs that could be translated into two or more proteins with different amino acid substitutions in a single individual. A fraction of the minor splice variants is predicted to be non-productive.
authors.affiliation: Molecular Diagnostics Laboratory, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA. Electronic address: susan.kirwin@nemours.org.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kirwin
authors.affiliation: Molecular Diagnostics Laboratory, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Athena
authors.initials: A
authors.lastname: Manolakos
authors.affiliation: Molecular Diagnostics Laboratory, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Sarah Swain
authors.initials: SS
authors.lastname: Barnett
authors.affiliation: Molecular Diagnostics Laboratory, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Iris L
authors.initials: IL
authors.lastname: Gonzalez
mesh_terms: D000217:Acyltransferases; D017398:Alternative Splicing; D019943:Amino Acid Substitution; D056889:Barth Syndrome / Q000235:genetics*; D001800:Blood Specimen Collection; D041321:Chromosomes, Human, X; D005091:Exons; D005260:Female; D006801:Humans; D007438:Introns; D008297:Male; D020125:Mutation, Missense; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D059368:RNA Isoforms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D059368:RNA Isoforms; D012333:RNA, Messenger; D014157:Transcription Factors; D000217:Acyltransferases; C108675:TAFAZZIN protein, human
keywords: 6-carboxyfluorescein, 5-6-FAM™; Alternative splicing; BTHS; Barth syndrome; CE; CL; Cardiolipin; DCM; Dilated cardiomyopathy; EBV; EDTA; Epstein–Barr virus; FAM; FL; HPLC; LVNC; MLCL; NHLBI; National Heart, Lung, and Blood Institute; PCR; PHA; RT; TAZ; Tafazzin; UTR; X-chromosome inactivation; XCI; capillary electrophoresis; cardiolipin; dilated cardiomyopathy; ethylenediaminetetraacetic acid; full length; high performance liquid chromatography; i-AAA protease; intermembrane-AAA protease; left ventricular noncompaction; monolysocardiolipin; phytohemagglutinin; polymerase chain reaction; reverse transcription; untranslated region