Mutation screening in Börjeson-Forssman-Lehmann syndrome: identification of a novel de novo PHF6 mutation in a female patient
- 1Department of Genetic Medicine, Women’s and Children’s Hospital, and Department of Paediatrics, University of Adelaide, Adelaide, Australia
- 2Clinical and Molecular Genetics Unit, Great Ormond Street Hospital for Children, London, UK
- 3Centre for Human Genetics, University Hospital Leuven, Leuven, Belgium
- 4Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon
- 5National Centre for Medical Genetics, Our Lady’s Hospital for Sick Children, Dublin, Ireland
- 6Hunter Genetics and University of Newcastle, New South Wales, Australia
- 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;
- Received 21 March 2005
- Accepted 23 June 2005
- Revised 21 June 2005
- Published Online First 1 July 2005
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
Published Online First 25 July 2005
Conflicts of interest: none declared