Human Genetics

, Volume 111, Issue 4, pp 368–375

A novel mutation in the IHH gene causes brachydactyly type A1: a 95-year-old mystery resolved

  • Elizabeth M. McCready
  • Elizabeth Sweeney
  • Allan E. Fryer
  • Dian Donnai
  • Akeel Baig
  • Lemuel Racacho
  • Matthew L. Warman
  • Alasdair G. Hunter
  • Dennis E. Bulman
Original Investigation

DOI: 10.1007/s00439-002-0815-2

Cite this article as:
McCready, E.M., Sweeney, E., Fryer, A.E. et al. Hum Genet (2002) 111: 368. doi:10.1007/s00439-002-0815-2

Abstract.

Brachydactyly type A1 (BDA1) was the first disorder described in terms of autosomal dominant Mendelian inheritance. Early in the 1900s Farabee and Drinkwater described a number of families with BDA1. Examination of two of Drinkwater's families has revealed that, although they are not known to be related, both share a common mutation within the Indian hedgehog gene (IHH). This novel mutation is a guanine to adenine transition at nucleotide 298, resulting in an Asn100Asp amino acid substitution. Both families demonstrate significant intrafamilial phenotypic heterogeneity among the affected individuals. Examination of single nucleotide polymorphisms (SNP) has shown that the affected individuals in both families share SNPs within IHH consistent with that of a common founder. The identification of the same mutation in these families has answered a question that is nearly a century old about the genetic cause of their disease and supports the hypothesis that IHH plays a pivotal role in normal human skeletogenesis.

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Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • Elizabeth M. McCready
    • 1
  • Elizabeth Sweeney
    • 4
  • Allan E. Fryer
    • 4
  • Dian Donnai
    • 5
  • Akeel Baig
    • 1
  • Lemuel Racacho
    • 1
  • Matthew L. Warman
    • 6
  • Alasdair G. Hunter
    • 8
  • Dennis E. Bulman
    • 1
  1. 1.Ottawa Health Research Institute, 501 Smyth Road, Rm. 4G-101, Ottawa, Ontario, Canada, K1H 8L6
  2. 2.University of Ottawa Centre for Neuromuscular Disease, Ottawa, Canada
  3. 3.Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada
  4. 4.Merseyside and Cheshire Clinical Genetics Service, Royal Liverpool Children's Hospital, Liverpool, UK
  5. 5.Academic Unit of Medical Genetics, University of Manchester, St Mary's Hospital, Manchester, UK
  6. 6.Department of Genetics and Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
  7. 7.Center for Human Genetics, University Hospital of Cleveland, Cleveland, Ohio, USA
  8. 8.Eastern Ontario Regional Genetics Program, Children's Hospital of Eastern Ontario, Ottawa, Canada
  9. 9.Department of Medicine, Division of Neurology, University of Ottawa, Ottawa, Canada

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