Mutations in PHF6 are associated with Börjeson-Forssman-Lehmann syndrome

Karen M. Lower; Gillian Turner; Bronwyn A. Kerr; Katherine D. Mathews; Marie A. Shaw; Ági 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 Ravenswaayl; Bert B.A. De Vries; Barbara Cox; Markus Grompe; Shelley Ross; Paul Thomas; John C. Mulley; Jozef Gécz

doi:10.1038/ng1040

Mutations in PHF6 are associated with Börjeson-Forssman-Lehmann syndrome

Karen M. Lower, Gillian Turner, Bronwyn A. Kerr, Katherine D. Mathews, Marie A. Shaw, Ági 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 Ravenswaayl, Bert B.A. De Vries, Barbara Cox, Markus Grompe, Shelley Ross, Paul Thomas, John C. MulleyJozef Gécz

Pediatrics

Research output: Contribution to journal › Article › peer-review

182 Scopus citations

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.

Original language	English (US)
Pages (from-to)	661-665
Number of pages	5
Journal	Nature genetics
Volume	32
Issue number	4
DOIs	https://doi.org/10.1038/ng1040
State	Published - Dec 1 2002

ASJC Scopus subject areas

Genetics

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Lower, K. M., Turner, G., Kerr, B. A., Mathews, K. D., Shaw, M. A., Gedeon, Á. K., Schelley, S., Hoyme, H. E., White, S. M., Delatycki, M. B., Lampe, A. K., Clayton-Smith, J., Stewart, H., Van Ravenswaayl, C. M. A., De Vries, B. B. A., Cox, B., Grompe, M., Ross, S., Thomas, P., ... Gécz, J. (2002). Mutations in PHF6 are associated with Börjeson-Forssman-Lehmann syndrome. Nature genetics, 32(4), 661-665. https://doi.org/10.1038/ng1040

Lower, KM, Turner, G, Kerr, BA, Mathews, KD, Shaw, MA, Gedeon, ÁK, Schelley, S, Hoyme, HE, White, SM, Delatycki, MB, Lampe, AK, Clayton-Smith, J, Stewart, H, Van Ravenswaayl, CMA, De Vries, BBA, Cox, B, Grompe, M, Ross, S, Thomas, P, Mulley, JC & Gécz, J 2002, 'Mutations in PHF6 are associated with Börjeson-Forssman-Lehmann syndrome', Nature genetics, vol. 32, no. 4, pp. 661-665. https://doi.org/10.1038/ng1040

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abstract = "B{\"o}rjeson-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.",

author = "Lower, {Karen M.} and Gillian Turner and Kerr, {Bronwyn A.} and Mathews, {Katherine D.} and Shaw, {Marie A.} and Gedeon, {{\'A}gi K.} and Susan Schelley and Hoyme, {H. Eugene} and White, {Susan M.} and Delatycki, {Martin B.} and Lampe, {Anne K.} and Jill Clayton-Smith and Helen Stewart and {Van Ravenswaayl}, {Conny M.A.} and {De Vries}, {Bert B.A.} and Barbara Cox and Markus Grompe and Shelley Ross and Paul Thomas and Mulley, {John C.} and Jozef G{\'e}cz",

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AU - Gedeon, Ági K.

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AU - Van Ravenswaayl, Conny M.A.

AU - De Vries, Bert B.A.

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AU - Grompe, Markus

AU - Ross, Shelley

AU - Thomas, Paul

AU - Mulley, John C.

AU - Gécz, Jozef

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N2 - 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.

AB - 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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Mutations in PHF6 are associated with Börjeson-Forssman-Lehmann syndrome

Abstract

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