Abstract
Börjeson–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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Acknowledgements
We thank the members of the families studied for their participation; C. Schwartz and J.P. Fryns for contributing samples; M. Lagerström Fermer for providing samples from the family affected with Gustavson syndrome; S. McDonnell and C. Derwas for help with cell culture; and M. Partington and G. Sutherland for critical reading of the manuscript. K.M.L. was supported by the Adelaide Research Scholarship from Adelaide University. This work was supported by the National Health and Medical Research Council of Australia.
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Lower, K., Turner, G., Kerr, B. et al. Mutations in PHF6 are associated with Börjeson–Forssman –Lehmann syndrome. Nat Genet 32, 661–665 (2002). https://doi.org/10.1038/ng1040
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DOI: https://doi.org/10.1038/ng1040
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