title: Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1.
abstract: Brachydactyly type A-1 (BDA-1; MIM 112500) is characterized by shortening or missing of the middle phalanges (Fig. 1a). It was first identified by Farabee in 1903 (ref. 2), is the first recorded example of a human anomaly with Mendelian autosomal-dominant inheritance and, as such, is cited in most genetic and biological textbooks. Here we show that mutations in IHH, which encodes Indian hedgehog, cause BDA-1. We have identified three heterozygous missense mutations in the region encoding the amino-terminal signaling domain in all affected members of three large, unrelated families. The three mutant amino acids, which are conserved across all vertebrates and invertebrates studied so far, are predicted to be adjacent on the surface of IHH.
authors.affiliation: Bio-X Life Science Research Center, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: B
authors.initials: B
authors.lastname: Gao
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: C
authors.initials: C
authors.lastname: She
authors.forename: A
authors.initials: A
authors.lastname: Shu
authors.forename: M
authors.initials: M
authors.lastname: Yang
authors.forename: Z
authors.initials: Z
authors.lastname: Tan
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: Guo
authors.forename: G
authors.initials: G
authors.lastname: Feng
authors.forename: L
authors.initials: L
authors.lastname: He
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D002681:China / Q000453:epidemiology; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D005799:Genes, Dominant; D006580:Genetic Carrier Screening; D006228:Hand Deformities, Congenital / Q000145:classification* / Q000453:epidemiology / Q000235:genetics*; D053823:Hedgehog Proteins; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D009626:Terminology as Topic; D015534:Trans-Activators
chemical_list: D053823:Hedgehog Proteins; D011506:Proteins; D015534:Trans-Activators