title: The human LMX1B gene: transcription unit, promoter, and pathogenic mutations.
abstract: LMX1B is a LIM-homeodomain transcription factor required for the normal development of dorsal limb structures, the glomerular basement membrane, the anterior segment of the eye, and dopaminergic and serotonergic neurons. Heterozygous loss-of-function mutations in LMX1B cause nail patella syndrome (NPS). To further understand LMX1B gene regulation and to identify pathogenic mutations within the coding region, a detailed analysis of LMX1B gene structure was undertaken. 5' -RACE and primer extension identified a long 5' -untranslated region of 1.3 kb that contains two upstream open-reading frames (uORFs). Transient transfection assays showed that sequences required for basal promoter activity extend no further than 112 bp upstream. An additional 47 mutations have been identified in the coding region, as well as nine deletions of large portions of the gene, but not in the promoter or highly conserved intronic sequences. The range of mutations and the identification of uORFs suggest further complexity in the regulation of LMX1B expression.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Dunston
authors.forename: Jeanette D
authors.initials: JD
authors.lastname: Hamlington
authors.forename: Jayshree
authors.initials: J
authors.lastname: Zaveri
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sweeney
authors.forename: Julie
authors.initials: J
authors.lastname: Sibbring
authors.forename: Catherine
authors.initials: C
authors.lastname: Tran
authors.forename: Maria
authors.initials: M
authors.lastname: Malbroux
authors.forename: John P
authors.initials: JP
authors.lastname: O'Neill
authors.forename: Roger
authors.initials: R
authors.lastname: Mountford
authors.forename: Iain
authors.initials: I
authors.lastname: McIntosh
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D004252:DNA Mutational Analysis; D017931:DNA Primers; D040461:Gene Components; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D008156:Luciferases; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000235:genetics*; D014162:Transfection
chemical_list: D017931:DNA Primers; D018398:Homeodomain Proteins; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; D008156:Luciferases