title: Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome.
abstract: Hand-foot-genital syndrome (HFGS) is a rare, dominantly inherited condition affecting the distal limbs and genitourinary tract. A nonsense mutation in the homeobox of HOXA13 has been identified in one affected family, making HFGS the second human syndrome shown to be caused by a HOX gene mutation. We have therefore examined HOXA13 in two new and four previously reported families with features of HFGS. In families 1, 2, and 3, nonsense mutations truncating the encoded protein N-terminal to or within the homeodomain produce typical limb and genitourinary abnormalities; in family 4, an expansion of an N-terminal polyalanine tract produces a similar phenotype; in family 5, a missense mutation, which alters an invariant domain, produces an exceptionally severe limb phenotype; and in family 6, in which limb abnormalities were atypical, no HOXA13 mutation could be detected. Mutations in HOXA13 can therefore cause more-severe limb abnormalities than previously suspected and may act by more than one mechanism.
authors.affiliation: Molecular Medicine Unit, Institute of Child Health, London, United Kingdom. fgoodman@hgmp.mrc.ac.uk
authors.forename: F R
authors.initials: FR
authors.lastname: Goodman
authors.forename: C
authors.initials: C
authors.lastname: Bacchelli
authors.forename: A F
authors.initials: AF
authors.lastname: Brady
authors.forename: L A
authors.initials: LA
authors.lastname: Brueton
authors.forename: J P
authors.initials: JP
authors.lastname: Fryns
authors.forename: D P
authors.initials: DP
authors.lastname: Mortlock
authors.forename: J W
authors.initials: JW
authors.lastname: Innis
authors.forename: L B
authors.initials: LB
authors.lastname: Holmes
authors.forename: A E
authors.initials: AE
authors.lastname: Donnenfeld
authors.forename: M
authors.initials: M
authors.lastname: Feingold
authors.forename: F A
authors.initials: FA
authors.lastname: Beemer
authors.forename: R C
authors.initials: RC
authors.lastname: Hennekam
authors.forename: P J
authors.initials: PJ
authors.lastname: Scambler
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging / Q000235:genetics*; D002648:Child; D018389:Codon, Nonsense / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005532:Foot Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics*; D005801:Genes, Homeobox / Q000235:genetics; D006228:Hand Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D011859:Radiography; D017384:Sequence Deletion / Q000235:genetics; D013577:Syndrome; D014564:Urogenital Abnormalities / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D018398:Homeodomain Proteins; C099959:homeobox protein HOXA13