title: PAX3 gene structure and mutations: close analogies between Waardenburg syndrome and the Splotch mouse.
abstract: The human PAX3 gene contains a paired box and a paired-type homeobox, and is believed to play a role in pattern formation in the embryo. We describe the exon-intron structure of the homeobox-containing part of PAX3, complementing earlier descriptions of the 5' part of the gene. Mutations in PAX3 have been described in patients with Type 1 Waardenburg syndrome, who have hearing loss and pigmentary abnormalities, while Splotch mice have mutations in the homologous mouse Pax-3 gene. We describe a series of patients who have previously unidentified PAX3 mutations. These include a chromosomal deletion, a splice-site mutation and an amino acid substitution which closely correspond to the molecular changes seen in the Splotch-retarded, Splotch and Splotch-delayed mouse mutants respectively. These mutations confirm that Waardenburg syndrome is produced by gene dosage effects and show that the phenotypic differences between Splotch mice and humans with Waardenburg syndrome are caused by differences in genetic background rather than different primary effects of the mutations.
authors.affiliation: Department of Medical Genetics, St Mary's Hospital, Manchester, UK.
authors.forename: M
authors.initials: M
authors.lastname: Tassabehji
authors.forename: V E
authors.initials: VE
authors.lastname: Newton
authors.forename: K
authors.initials: K
authors.lastname: Leverton
authors.forename: K
authors.initials: K
authors.lastname: Turnbull
authors.forename: E
authors.initials: E
authors.lastname: Seemanova
authors.forename: J
authors.initials: J
authors.lastname: Kunze
authors.forename: K
authors.initials: K
authors.lastname: Sperling
authors.forename: T
authors.initials: T
authors.lastname: Strachan
authors.forename: A P
authors.initials: AP
authors.lastname: Read
mesh_terms: D000818:Animals; D001483:Base Sequence; D002465:Cell Movement; D002889:Chromosomes, Human, Pair 2; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D005796:Genes; D005801:Genes, Homeobox; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics*; D008969:Molecular Sequence Data; D009432:Neural Crest / Q000473:pathology; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D010641:Phenotype; D017354:Point Mutation; D012326:RNA Splicing; D017384:Sequence Deletion; D013045:Species Specificity; D014157:Transcription Factors; D014849:Waardenburg Syndrome / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse