title: Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome.
abstract: Ulnar-mammary syndrome is a rare pleiotropic disorder affecting limb, apocrine gland, tooth and genital development. We demonstrate that mutations in human TBX3, a member of the T-box gene family, cause ulnar-mammary syndrome in two families. Each mutation (a single nucleotide deletion and a splice-site mutation) is predicted to cause haploinsufficiency of TBX3, implying that critical levels of this transcription factor are required for morphogenesis of several organs. Limb abnormalities of ulnar-mammary syndrome involve posterior elements. Mutations in TBX5, a related and linked gene, cause anterior limb abnormalities in Holt-Oram syndrome. We suggest that during the evolution of TBX3 and TBX5 from a common ancestral gene, each has acquired specific yet complementary roles in patterning the mammalian upper limb.
authors.affiliation: Department of Pediatrics, University of Utah Health Sciences Center, Salt Lake City 84112, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bamshad
authors.forename: R C
authors.initials: RC
authors.lastname: Lin
authors.forename: D J
authors.initials: DJ
authors.lastname: Law
authors.forename: W C
authors.initials: WC
authors.lastname: Watkins
authors.forename: P A
authors.initials: PA
authors.lastname: Krakowiak
authors.forename: M E
authors.initials: ME
authors.lastname: Moore
authors.forename: P
authors.initials: P
authors.lastname: Franceschini
authors.forename: R
authors.initials: R
authors.lastname: Lala
authors.forename: L B
authors.initials: LB
authors.lastname: Holmes
authors.forename: T C
authors.initials: TC
authors.lastname: Gebuhr
authors.forename: B G
authors.initials: BG
authors.lastname: Bruneau
authors.forename: A
authors.initials: A
authors.lastname: Schinzel
authors.forename: J G
authors.initials: JG
authors.lastname: Seidman
authors.forename: C E
authors.initials: CE
authors.lastname: Seidman
authors.forename: L B
authors.initials: LB
authors.lastname: Jorde
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D001050:Apocrine Glands / Q000002:abnormalities*; D001132:Arm / Q000002:abnormalities*; D001483:Base Sequence; D001940:Breast / Q000002:abnormalities; D002881:Chromosomes, Human, Pair 12; D004252:DNA Mutational Analysis; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005835:Genitalia / Q000002:abnormalities*; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D013577:Syndrome; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*
chemical_list: D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; C106884:TBX3 protein, human; D014157:Transcription Factors