Human Genetics

, Volume 109, Issue 6, pp 638–645

Hemifacial microsomia: progress in understanding the genetic basis of a complex malformation syndrome

  • D. Kelberman
  • J. Tyson
  • D. Chandler
  • A. McInerney
  • J. Slee
  • D. Albert
  • A. Aymat
  • M. Botma
  • M. Calvert
  • J. Goldblatt
  • E. Haan
  • N. Laing
  • J. Lim
  • S. Malcolm
  • S. Singer
  • R. Winter
  • M. Bitner-Glindzicz
Original Investigation

DOI: 10.1007/s00439-001-0626-x

Cite this article as:
Kelberman, D., Tyson, J., Chandler, D. et al. Hum Genet (2001) 109: 638. doi:10.1007/s00439-001-0626-x

Abstract.

Hemifacial microsomia (HFM) is a common birth defect involving first and second branchial arch derivatives. The phenotype is extremely variable. In addition to craniofacial anomalies there may be cardiac, vertebral and central nervous system defects. The majority of cases are sporadic, but there is substantial evidence for genetic involvement in this condition, including rare familial cases that exhibit autosomal dominant inheritance. As an approach towards identifying molecular pathways involved in ear and facial development, we have ascertained both familial and sporadic cases of HFM. A genome wide search for linkage in two families with features of HFM was performed to identify the disease loci. In one family data were highly suggestive of linkage to a region of approximately 10.7 cM on chromosome 14q32, with a maximum multipoint lod score of 3.00 between microsatellite markers D14S987 and D14S65. This locus harbours the Goosecoid gene, an excellent candidate for HFM based on mouse expression and phenotype data. Coding region mutations were sought in the familial cases and in 120 sporadic cases, and gross rearrangements of the gene were excluded by Southern blotting. Evidence for genetic heterogeneity is provided by the second family, in which linkage was excluded from this region.

Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • D. Kelberman
    • 1
  • J. Tyson
    • 1
  • D. Chandler
    • 2
  • A. McInerney
    • 1
  • J. Slee
    • 3
  • D. Albert
    • 4
  • A. Aymat
    • 4
  • M. Botma
    • 4
  • M. Calvert
    • 5
  • J. Goldblatt
    • 3
  • E. Haan
    • 6
  • N. Laing
    • 2
  • J. Lim
    • 4
  • S. Malcolm
    • 1
  • S. Singer
    • 7
  • R. Winter
    • 1
  • M. Bitner-Glindzicz
    • 1
  1. 1.Clinical and Molecular Genetics Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UKUK
  2. 2.Australian Neuromuscular Research Institute, QE II Medical Centre, Needlands, Western Australia, AustraliaAustralia
  3. 3.Genetic Services, King Edward Memorial Hospital, Western Australia, AustraliaAustralia
  4. 4.ENT Department, Great Ormond Street Hospital for Children NHS Trust, London, WC1N 3JH, UKUK
  5. 5.Maxillofacial and Dental Department, Great Ormond Street Hospital for Children NHS Trust, London, WC1N 3JH, UKUK
  6. 6.South Australian Clinical Genetics Service, Women's and Children's Hospital, North Adelaide, South Australia, AustraliaAustralia
  7. 7.Dental Department, Princess Margaret Hospital for Children, Subiaco, Western Australia, AustraliaAustralia