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

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

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
Pages (from-to)	661-665
Number of pages	4
Journal	Nature Genetics
Volume	32
Issue number	4
DOIs	https://doi.org/10.1038/ng1040
Publication status	Published - 1 Dec 2002

Keywords

Amino Acid Motifs
Amino Acid Sequence
Amino Acid Substitution
Animals
metabolism: Cell Nucleolus
metabolism: Cell Nucleus
metabolism: Embryo
Female
Genetic Predisposition to Disease
Green Fluorescent Proteins
Hela Cells
Heterozygote
Humans
metabolism: Luminescent Proteins
Male
genetics: Mental Retardation
Mice
Microsatellite Repeats
Molecular Sequence Data
Mutation
Mutation, Missense
Pedigree
Physical Chromosome Mapping
Research Support, Non-U.S. Gov't
Sequence Alignment
Syndrome
Transfection
X Chromosome
Zinc Fingers

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng1040

Cite this

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

@article{b710868410b949eca9545281110fa26a,

title = "Mutations in PHF6 are associated with B{\"o}rjeson-Forssman-Lehmann syndrome",

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.",

keywords = "Amino Acid Motifs, Amino Acid Sequence, Amino Acid Substitution, Animals, metabolism: Cell Nucleolus, metabolism: Cell Nucleus, metabolism: Embryo, Female, Genetic Predisposition to Disease, Green Fluorescent Proteins, Hela Cells, Heterozygote, Humans, metabolism: Luminescent Proteins, Male, genetics: Mental Retardation, Mice, Microsatellite Repeats, Molecular Sequence Data, Mutation, Mutation, Missense, Pedigree, Physical Chromosome Mapping, Research Support, Non-U.S. Gov't, Sequence Alignment, Syndrome, Transfection, X Chromosome, Zinc Fingers",

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",

year = "2002",

month = dec,

day = "1",

doi = "10.1038/ng1040",

language = "English",

volume = "32",

pages = "661--665",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "4",

}

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

TY - JOUR

T1 - Mutations in PHF6 are associated with Börjeson-Forssman-Lehmann syndrome

AU - Lower, Karen M.

AU - Turner, Gillian

AU - Kerr, Bronwyn A.

AU - Mathews, Katherine D.

AU - Shaw, Marie A.

AU - Gedeon, Ági K.

AU - Schelley, Susan

AU - Hoyme, H. Eugene

AU - White, Susan M.

AU - Delatycki, Martin B.

AU - Lampe, Anne K.

AU - Clayton-Smith, Jill

AU - Stewart, Helen

AU - Van Ravenswaayl, Conny M A

AU - De Vries, Bert B A

AU - Cox, Barbara

AU - Grompe, Markus

AU - Ross, Shelley

AU - Thomas, Paul

AU - Mulley, John C.

AU - Gécz, Jozef

PY - 2002/12/1

Y1 - 2002/12/1

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.

KW - Amino Acid Motifs

KW - Amino Acid Sequence

KW - Amino Acid Substitution

KW - Animals

KW - metabolism: Cell Nucleolus

KW - metabolism: Cell Nucleus

KW - metabolism: Embryo

KW - Female

KW - Genetic Predisposition to Disease

KW - Green Fluorescent Proteins

KW - Hela Cells

KW - Heterozygote

KW - Humans

KW - metabolism: Luminescent Proteins

KW - Male

KW - genetics: Mental Retardation

KW - Mice

KW - Microsatellite Repeats

KW - Molecular Sequence Data

KW - Mutation

KW - Mutation, Missense

KW - Pedigree

KW - Physical Chromosome Mapping

KW - Research Support, Non-U.S. Gov't

KW - Sequence Alignment

KW - Syndrome

KW - Transfection

KW - X Chromosome

KW - Zinc Fingers

U2 - 10.1038/ng1040

DO - 10.1038/ng1040

M3 - Article

SN - 1061-4036

VL - 32

SP - 661

EP - 665

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

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

Abstract

Keywords

UN SDGs

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