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.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • February 2007

Published In

Volume / Issue

  • 80 / 2

Start / End Page

  • 345 - 352

PubMed ID

  • 17236139

Pubmed Central ID

  • PMC1785336

International Standard Serial Number (ISSN)

  • 0002-9297

Digital Object Identifier (DOI)

  • 10.1086/511134


  • eng

Conference Location

  • United States