Mutation in CUL4B, which encodes a member of cullin-RING ubiquitin ligase complex, causes X-linked mental retardation

Yongxin Zou, Qiji Liu, Bingxi Chen, Xiyu Zhang, Chenhong Guo, Haibin Zhou, Jiangxia Li, Guimin Gao, Yishou Guo, Chuanzhu Yan, Jianjun Wei, Changshun Shao, Yaoqin Gong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

We reevaluated a previously reported family with an X-linked mental retardation syndrome and attempted to identify the underlying genetic defect. Screening of candidate genes in a 10-Mb region on Xq25 implicated CUL4B as the causative gene. CUL4B encodes a scaffold protein that organizes a cullin-RING (really interesting new gene) ubiquitin ligase (E3) complex in ubiquitylation. A base substitution, c.l564C→T, converted a codon for arginine into a premature termination codon, p.R388X, and rendered the truncated peptide completely devoid of the C-terminal catalytic domain. The nonsense mutation also results in nonsense-mediated mRNA decay in patients. In peripheral leukocytes of obligate carriers, a strong selection against cells expressing the mutant allele results in an extremely skewed X-chromosome inactivation pattern. Our findings point to the functional significance of CUL4B in cognition and in other aspects of human development.

Original languageEnglish (US)
Pages (from-to)561-566
Number of pages6
JournalAmerican journal of human genetics
Volume80
Issue number3
DOIs
StatePublished - Mar 2007

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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