Nature Genetics
32, 661 - 665 (2002)
Published online: 4 November 2002; | doi:10.1038/ng1040
Mutations in PHF6 are associated with
Börjeson−Forssman
−Lehmann syndromeKaren M. Lower1, 2, Gillian Turner3, Bronwyn A. Kerr4, Katherine D. Mathews5, Marie A. Shaw1, Ági K. Gedeon1, Susan Schelley6, H. Eugene Hoyme6, Susan M. White7, Martin B. Delatycki7, Anne K. Lampe8, Jill Clayton-Smith4, Helen Stewart9, Conny M. A. van Ravenswaay10, Bert B. A. de Vries10, Barbara Cox11, Markus Grompe11, Shelley Ross12, Paul Thomas12, John C. Mulley1, 13
& Jozef Gécz1, 21
Department of Cytogenetics and Molecular Genetics, Centre for Medical Genetics, Women's and Children's Hospital, 72 King William Rd., North Adelaide, SA 5006, Australia. 2
Department of Paediatrics, University of Adelaide, Adelaide, SA 5001, Australia. 3
Hunter Genetics and University of Newcastle, New South Wales, Waratah, Australia. 4
Regional Genetic Service, St. Mary's Hospital, Manchester, UK. 5
Department of Pediatrics and Neurology, University of Iowa Hospital and Clinics, Iowa City, Iowa, USA. 6
Division of Medical Genetics, Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA. 7
Genetic Health Services Victoria, Royal Children's Hospital, Melbourne, Victoria, Australia. 8
Department of Clinical Genetics, Institute of Human Genetics, International Centre for Life, Central Parkway, Newcastle upon Tyne, UK. 9
Department of Medical Genetics, Churchill Hospital, Old Road, Headington, Oxford, UK. 10
Department of Human Genetics, University Medical Centre, Nijmegen, The Netherlands. 11
Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland, Oregon, USA. 12
Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia. 13
Department of Molecular Biosciences, University of Adelaide, Adelaide, Australia.
Correspondence should be addressed to Jozef Gécz jozef.gecz@adelaide.edu.auBörjeson−Forssman−Lehmann syndrome (BFLS; OMIM 301900) is characterized by moderate to severe mental retardation, epilepsy, hypogonadism, hypometabolism, obesity with marked gynecomastia, swelling of subcutaneous tissue of the face, narrow palpebral fissure and large but not deformed ears1. Previously, the gene associated with BFLS was localized to 17 Mb in Xq26−q27 (refs 2−4). We have reduced this interval to roughly 9 Mb containing more than 62 genes. Among these, a novel, widely expressed zinc-finger (plant homeodomain (PHD)-like finger) gene (PHF6) had eight different missense and truncation mutations in seven familial and two sporadic cases of BFLS. Transient transfection studies with PHF6 tagged with green fluorescent protein (GFP) showed diffuse nuclear staining with prominent nucleolar accumulation. Such localization, and the presence of two PHD-like zinc fingers, is suggestive of a role for PHF6 in transcription.
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