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Mutation screening in Börjeson-Forssman-Lehmann syndrome: identification of a novel de novo PHF6 mutation in a female patient
  1. J Crawford1,
  2. K M Lower1,
  3. R C M Hennekam2,
  4. H Van Esch3,
  5. A Mégarbané4,
  6. S A Lynch5,
  7. G Turner6,
  8. J Gécz1
  1. 1Department of Genetic Medicine, Women’s and Children’s Hospital, and Department of Paediatrics, University of Adelaide, Adelaide, Australia
  2. 2Clinical and Molecular Genetics Unit, Great Ormond Street Hospital for Children, London, UK
  3. 3Centre for Human Genetics, University Hospital Leuven, Leuven, Belgium
  4. 4Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon
  5. 5National Centre for Medical Genetics, Our Lady’s Hospital for Sick Children, Dublin, Ireland
  6. 6Hunter Genetics and University of Newcastle, New South Wales, Australia
  1. Correspondence to:
 A/Prof Jozef Gécz
 Department of Genetic Medicine, Women’s and Children’s Hospital, 72 King William Road, North Adelaide, SA 5006, Australia; jozef.gecz{at}


Background: Börjeson-Forssman-Lehmann syndrome (BFLS; MIM 301900) is an infrequently described X linked disorder caused by mutations in PHF6, a novel zinc finger gene of unknown function.

Objective: To present the results of mutation screening in individuals referred for PHF6 testing and discuss the value of prior X-inactivation testing in the mothers of these individuals.

Results: 25 unrelated individuals were screened (24 male, one female). Five PHF6 mutations were detected, two of which (c.940A→G and c.27_28insA) were novel. One of these new mutations, c.27_28insA, was identified in a female BFLS patient. This was shown to be a de novo mutation arising on the paternal chromosome. This is the first report of a clinically diagnosed BFLS female with a confirmed PHF6 mutation. In addition, the X-inactivation status of the mothers of 19 males with suggested clinical diagnosis of BFLS was determined. Skewed (⩾70%) X-inactivation was present in five mothers, three of whom had sons in whom a PHF6 mutation was detected. The mutation positive female also showed skewing.

Conclusions: The results indicate that the success of PHF6 screening in males suspected of having BFLS is markedly increased if there is a positive family history and/or skewed X-inactivation is found in the mother.

  • AR, androgen receptor
  • BFLS, Börjeson-Forssman-Lehmann syndrome
  • ORF, open reading frame
  • XLMR, X linked mental retardation
  • BFLS
  • PHF6
  • mutation summary
  • skewed X-inactivation

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  • Published Online First 25 July 2005

  • Conflicts of interest: none declared