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 (> or =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.
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 BFLSpatient. 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 (> or =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.
Authors: Karen M Lower; Gillian Turner; Bronwyn A Kerr; Katherine D Mathews; Marie A Shaw; Agi K Gedeon; Susan Schelley; H Eugene Hoyme; Susan M White; Martin B Delatycki; Anne K Lampe; Jill Clayton-Smith; Helen Stewart; Conny M A van Ravenswaay; Bert B A de Vries; Barbara Cox; Markus Grompe; Shelley Ross; Paul Thomas; John C Mulley; Jozef Gécz Journal: Nat Genet Date: 2002-11-04 Impact factor: 38.330
Authors: G Turner; K M Lower; S M White; M Delatycki; A K Lampe; M Wright; J Clayton Smith; B Kerr; S Schelley; H E Hoyme; B B A De Vries; T Kleefstra; M Grompe; B Cox; J Gecz; M Partington Journal: Clin Genet Date: 2004-03 Impact factor: 4.438
Authors: Anna Hackett; Patrick S Tarpey; Andrea Licata; James Cox; Annabel Whibley; Jackie Boyle; Carolyn Rogers; John Grigg; Michael Partington; Roger E Stevenson; John Tolmie; John Rw Yates; Gillian Turner; Meredith Wilson; Andrew P Futreal; Mark Corbett; Marie Shaw; Jozef Gecz; F Lucy Raymond; Michael R Stratton; Charles E Schwartz; Fatima E Abidi Journal: Eur J Hum Genet Date: 2009-12-23 Impact factor: 4.246
Authors: Anja Ernst; Vang Q Le; Allan T Højland; Inge S Pedersen; Tine H Sørensen; Lise L Bjerregaard; Troels J B Lyngbye; Ninna M Gammelager; Henrik Krarup; Michael B Petersen Journal: Mol Syndromol Date: 2015-09-29