Mutation screening in Börjeson-Forssman-Lehmann syndrome: Identification of a novel de novo PHF6 mutation in a female patient

J. Crawford, K. M. Lower, R. C.M. Hennekam, H. Van Esch, A. Mégarbané, S. Ann Lynch, G. Turner, Jozef Gécz

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages238-243
Number of pages6
JournalJournal of Medical Genetics
Volume43
Issue number3
DOIs
Publication statusPublished - 1 Mar 2006

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Crawford, J. ; Lower, K. M. ; Hennekam, R. C.M. ; Van Esch, H. ; Mégarbané, A. ; Lynch, S. Ann ; Turner, G. ; Gécz, Jozef. / Mutation screening in Börjeson-Forssman-Lehmann syndrome : Identification of a novel de novo PHF6 mutation in a female patient. In: Journal of Medical Genetics. 2006 ; Vol. 43, No. 3. pp. 238-243.
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abstract = "Background: B{\"o}rjeson-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.",
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Mutation screening in Börjeson-Forssman-Lehmann syndrome : Identification of a novel de novo PHF6 mutation in a female patient. / Crawford, J.; Lower, K. M.; Hennekam, R. C.M.; Van Esch, H.; Mégarbané, A.; Lynch, S. Ann; Turner, G.; Gécz, Jozef.

In: Journal of Medical Genetics, Vol. 43, No. 3, 01.03.2006, p. 238-243.

Research output: Contribution to journalArticle

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T1 - Mutation screening in Börjeson-Forssman-Lehmann syndrome

T2 - Journal of medical genetics

AU - Crawford, J.

AU - Lower, K. M.

AU - Hennekam, R. C.M.

AU - Van Esch, H.

AU - Mégarbané, A.

AU - Lynch, S. Ann

AU - Turner, G.

AU - Gécz, Jozef

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