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 MenziesTatiana 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

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165 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)345-352
Number of pages8
JournalAmerican Journal of Human Genetics
Issue number2
Publication statusPublished or Issued - Feb 2007
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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