title: Brachydactyly A-1 mutations restricted to the central region of the N-terminal active fragment of Indian Hedgehog.
abstract: Mutations in the gene Indian Hedgehog (IHH) that cause Brachydactyly A-1 (BDA1) have been restricted to a specific region of the N-terminal active fragment of Indian Hedgehog involving codons 95, 100, 131, and 154. We describe two novel mutations in codons 128 and 130, not previously implicated in BDA1. Furthermore, we identified an independent mutation at codon 131 and we also describe a New Zealand family, which carries the 'Farabee' founder mutation and haplotype. All of the BDA1 mutations occur in a restricted area of the N-terminal active fragment of the IHH and are in contrast to those mutations causing an autosomal recessive acrocapitofemoral dysplasia, whose mutations are located at the distal N- and C-terminal regions of IHH-N and are physically separated from the BDA1-causing mutations. The identification of multiple independent mutations in codons 95, 100, and now in 131, implicate a discrete function for this region of the protein. Finally, we present a clinical review of all reported and confirmed cases of BDA1, highlighting features of the disorder, which add to the spectrum of the IHH mutations.
authors.affiliation: Ottawa Health Research Institute, Ottawa, Ontario, Canada.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Byrnes
authors.forename: Lemuel
authors.initials: L
authors.lastname: Racacho
authors.forename: Allison
authors.initials: A
authors.lastname: Grimsey
authors.forename: Louanne
authors.initials: L
authors.lastname: Hudgins
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Kwan
authors.forename: Michel
authors.initials: M
authors.lastname: Sangalli
authors.forename: Alexa
authors.initials: A
authors.lastname: Kidd
authors.forename: Yuval
authors.initials: Y
authors.lastname: Yaron
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Nikkel
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Bulman
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D018703:Founder Effect; D006228:Hand Deformities, Congenital / Q000235:genetics* / Q000473:pathology; D053823:Hedgehog Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009520:New Zealand; D010375:Pedigree; D017386:Sequence Homology, Amino Acid
chemical_list: D003062:Codon; D053823:Hedgehog Proteins; C509246:IHH protein, human