Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor

Patrick S. Tarpey, F. Lucy Raymond, Sarah O'Meara, Sarah Edkins, Jon Teague, Adam Butler, Ed Dicks, Claire Stevens, Calli Tofts, Tim Avis, Syd Barthorpe, Gemma Buck, Jennifer Cole, Kristian Gray, Kelly Halliday, Rachel Harrison, Katy Hills, Andrew Jenkinson, David Jones, Andrew Menzies & 33 others Tatiana Mironenko, Janet Perry, Keiran Raine, David Richardson, Rebecca Shepherd, Alexandra Small, Jennifer Varian, Sofie West, Sara Widaa, Uma Mallya, Jenny Moon, Ying Luo, Susan Holder, Sarah F. Smithson, Jane A. Hurst, Jill Clayton-Smith, Bronwyn Kerr, Jackie Boyle, Marie Shaw, Lucianne Vandeleur, Jayson Rodriguez, Rachel Slaugh, Douglas F. Easton, Richard Wooster, Martin Bobrow, Anand K. Srivastava, Roger E. Stevenson, Charles E. Schwartz, Gillian Turner, Jozef Gecz, P. Andrew Futreal, Michael R. Stratton, Michael Partington

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

We have identified three truncating, two splice-site, and three missense variants at conserved amino acids in the CUL4B gene on Xq24 in 8 of 250 families with X-linked mental retardation (XLMR). During affected subjects' adolescence, a syndrome emerged with delayed puberty, hypogonadism, relative macrocephaly, moderate short stature, central obesity, unprovoked aggressive outbursts, fine intention tremor, pes cavus, and abnormalities of the toes. This syndrome was first described by Cazebas et al., in a family that was included in our study and that carried a CUL4B missense variant. CUL4B is a ubiquitin E3 ligase subunit implicated in the regulation of several biological processes, and CUL4B is the first XLMR gene that encodes an E3 ubiquitin ligase. The relatively high frequency of CUL4B mutations in this series indicates that it is one of the most commonly mutated genes underlying XLMR and suggests that its introduction into clinical diagnostics should be a high priority.

LanguageEnglish
Pages345-352
Number of pages8
JournalAmerican Journal of Human Genetics
Volume80
Issue number2
DOIs
Publication statusPublished - 1 Jan 2007
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Tarpey, Patrick S. ; Raymond, F. Lucy ; O'Meara, Sarah ; Edkins, Sarah ; Teague, Jon ; Butler, Adam ; Dicks, Ed ; Stevens, Claire ; Tofts, Calli ; Avis, Tim ; Barthorpe, Syd ; Buck, Gemma ; Cole, Jennifer ; Gray, Kristian ; Halliday, Kelly ; Harrison, Rachel ; Hills, Katy ; Jenkinson, Andrew ; Jones, David ; Menzies, Andrew ; Mironenko, Tatiana ; Perry, Janet ; Raine, Keiran ; Richardson, David ; Shepherd, Rebecca ; Small, Alexandra ; Varian, Jennifer ; West, Sofie ; Widaa, Sara ; Mallya, Uma ; Moon, Jenny ; Luo, Ying ; Holder, Susan ; Smithson, Sarah F. ; Hurst, Jane A. ; Clayton-Smith, Jill ; Kerr, Bronwyn ; Boyle, Jackie ; Shaw, Marie ; Vandeleur, Lucianne ; Rodriguez, Jayson ; Slaugh, Rachel ; Easton, Douglas F. ; Wooster, Richard ; Bobrow, Martin ; Srivastava, Anand K. ; Stevenson, Roger E. ; Schwartz, Charles E. ; Turner, Gillian ; Gecz, Jozef ; Futreal, P. Andrew ; Stratton, Michael R. ; Partington, Michael. / Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor. In: American Journal of Human Genetics. 2007 ; Vol. 80, No. 2. pp. 345-352.
@article{294390d69f7349dab75803e68eaeb81e,
title = "Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor",
abstract = "We have identified three truncating, two splice-site, and three missense variants at conserved amino acids in the CUL4B gene on Xq24 in 8 of 250 families with X-linked mental retardation (XLMR). During affected subjects' adolescence, a syndrome emerged with delayed puberty, hypogonadism, relative macrocephaly, moderate short stature, central obesity, unprovoked aggressive outbursts, fine intention tremor, pes cavus, and abnormalities of the toes. This syndrome was first described by Cazebas et al., in a family that was included in our study and that carried a CUL4B missense variant. CUL4B is a ubiquitin E3 ligase subunit implicated in the regulation of several biological processes, and CUL4B is the first XLMR gene that encodes an E3 ubiquitin ligase. The relatively high frequency of CUL4B mutations in this series indicates that it is one of the most commonly mutated genes underlying XLMR and suggests that its introduction into clinical diagnostics should be a high priority.",
author = "Tarpey, {Patrick S.} and Raymond, {F. Lucy} and Sarah O'Meara and Sarah Edkins and Jon Teague and Adam Butler and Ed Dicks and Claire Stevens and Calli Tofts and Tim Avis and Syd Barthorpe and Gemma Buck and Jennifer Cole and Kristian Gray and Kelly Halliday and Rachel Harrison and Katy Hills and Andrew Jenkinson and David Jones and Andrew Menzies and Tatiana Mironenko and Janet Perry and Keiran Raine and David Richardson and Rebecca Shepherd and Alexandra Small and Jennifer Varian and Sofie West and Sara Widaa and Uma Mallya and Jenny Moon and Ying Luo and Susan Holder and Smithson, {Sarah F.} and Hurst, {Jane A.} and Jill Clayton-Smith and Bronwyn Kerr and Jackie Boyle and Marie Shaw and Lucianne Vandeleur and Jayson Rodriguez and Rachel Slaugh and Easton, {Douglas F.} and Richard Wooster and Martin Bobrow and Srivastava, {Anand K.} and Stevenson, {Roger E.} and Schwartz, {Charles E.} and Gillian Turner and Jozef Gecz and Futreal, {P. Andrew} and Stratton, {Michael R.} and Michael Partington",
year = "2007",
month = "1",
day = "1",
doi = "10.1086/511134",
language = "English",
volume = "80",
pages = "345--352",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "2",

}

Tarpey, PS, Raymond, FL, O'Meara, S, Edkins, S, Teague, J, Butler, A, Dicks, E, Stevens, C, Tofts, C, Avis, T, Barthorpe, S, Buck, G, Cole, J, Gray, K, Halliday, K, Harrison, R, Hills, K, Jenkinson, A, Jones, D, Menzies, A, Mironenko, T, Perry, J, Raine, K, Richardson, D, Shepherd, R, Small, A, Varian, J, West, S, Widaa, S, Mallya, U, Moon, J, Luo, Y, Holder, S, Smithson, SF, Hurst, JA, Clayton-Smith, J, Kerr, B, Boyle, J, Shaw, M, Vandeleur, L, Rodriguez, J, Slaugh, R, Easton, DF, Wooster, R, Bobrow, M, Srivastava, AK, Stevenson, RE, Schwartz, CE, Turner, G, Gecz, J, Futreal, PA, Stratton, MR & Partington, M 2007, 'Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor', American Journal of Human Genetics, vol. 80, no. 2, pp. 345-352. https://doi.org/10.1086/511134

Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor. / Tarpey, Patrick S.; Raymond, F. Lucy; O'Meara, Sarah; Edkins, Sarah; Teague, Jon; Butler, Adam; Dicks, Ed; Stevens, Claire; Tofts, Calli; Avis, Tim; Barthorpe, Syd; Buck, Gemma; Cole, Jennifer; Gray, Kristian; Halliday, Kelly; Harrison, Rachel; Hills, Katy; Jenkinson, Andrew; Jones, David; Menzies, Andrew; Mironenko, Tatiana; Perry, Janet; Raine, Keiran; Richardson, David; Shepherd, Rebecca; Small, Alexandra; Varian, Jennifer; West, Sofie; Widaa, Sara; Mallya, Uma; Moon, Jenny; Luo, Ying; Holder, Susan; Smithson, Sarah F.; Hurst, Jane A.; Clayton-Smith, Jill; Kerr, Bronwyn; Boyle, Jackie; Shaw, Marie; Vandeleur, Lucianne; Rodriguez, Jayson; Slaugh, Rachel; Easton, Douglas F.; Wooster, Richard; Bobrow, Martin; Srivastava, Anand K.; Stevenson, Roger E.; Schwartz, Charles E.; Turner, Gillian; Gecz, Jozef; Futreal, P. Andrew; Stratton, Michael R.; Partington, Michael.

In: American Journal of Human Genetics, Vol. 80, No. 2, 01.01.2007, p. 345-352.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor

AU - Tarpey, Patrick S.

AU - Raymond, F. Lucy

AU - O'Meara, Sarah

AU - Edkins, Sarah

AU - Teague, Jon

AU - Butler, Adam

AU - Dicks, Ed

AU - Stevens, Claire

AU - Tofts, Calli

AU - Avis, Tim

AU - Barthorpe, Syd

AU - Buck, Gemma

AU - Cole, Jennifer

AU - Gray, Kristian

AU - Halliday, Kelly

AU - Harrison, Rachel

AU - Hills, Katy

AU - Jenkinson, Andrew

AU - Jones, David

AU - Menzies, Andrew

AU - Mironenko, Tatiana

AU - Perry, Janet

AU - Raine, Keiran

AU - Richardson, David

AU - Shepherd, Rebecca

AU - Small, Alexandra

AU - Varian, Jennifer

AU - West, Sofie

AU - Widaa, Sara

AU - Mallya, Uma

AU - Moon, Jenny

AU - Luo, Ying

AU - Holder, Susan

AU - Smithson, Sarah F.

AU - Hurst, Jane A.

AU - Clayton-Smith, Jill

AU - Kerr, Bronwyn

AU - Boyle, Jackie

AU - Shaw, Marie

AU - Vandeleur, Lucianne

AU - Rodriguez, Jayson

AU - Slaugh, Rachel

AU - Easton, Douglas F.

AU - Wooster, Richard

AU - Bobrow, Martin

AU - Srivastava, Anand K.

AU - Stevenson, Roger E.

AU - Schwartz, Charles E.

AU - Turner, Gillian

AU - Gecz, Jozef

AU - Futreal, P. Andrew

AU - Stratton, Michael R.

AU - Partington, Michael

PY - 2007/1/1

Y1 - 2007/1/1

N2 - We have identified three truncating, two splice-site, and three missense variants at conserved amino acids in the CUL4B gene on Xq24 in 8 of 250 families with X-linked mental retardation (XLMR). During affected subjects' adolescence, a syndrome emerged with delayed puberty, hypogonadism, relative macrocephaly, moderate short stature, central obesity, unprovoked aggressive outbursts, fine intention tremor, pes cavus, and abnormalities of the toes. This syndrome was first described by Cazebas et al., in a family that was included in our study and that carried a CUL4B missense variant. CUL4B is a ubiquitin E3 ligase subunit implicated in the regulation of several biological processes, and CUL4B is the first XLMR gene that encodes an E3 ubiquitin ligase. The relatively high frequency of CUL4B mutations in this series indicates that it is one of the most commonly mutated genes underlying XLMR and suggests that its introduction into clinical diagnostics should be a high priority.

AB - We have identified three truncating, two splice-site, and three missense variants at conserved amino acids in the CUL4B gene on Xq24 in 8 of 250 families with X-linked mental retardation (XLMR). During affected subjects' adolescence, a syndrome emerged with delayed puberty, hypogonadism, relative macrocephaly, moderate short stature, central obesity, unprovoked aggressive outbursts, fine intention tremor, pes cavus, and abnormalities of the toes. This syndrome was first described by Cazebas et al., in a family that was included in our study and that carried a CUL4B missense variant. CUL4B is a ubiquitin E3 ligase subunit implicated in the regulation of several biological processes, and CUL4B is the first XLMR gene that encodes an E3 ubiquitin ligase. The relatively high frequency of CUL4B mutations in this series indicates that it is one of the most commonly mutated genes underlying XLMR and suggests that its introduction into clinical diagnostics should be a high priority.

UR - http://www.scopus.com/inward/record.url?scp=33846639529&partnerID=8YFLogxK

U2 - 10.1086/511134

DO - 10.1086/511134

M3 - Article

VL - 80

SP - 345

EP - 352

JO - American Journal of Human Genetics

T2 - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 2

ER -