Journal
AMERICAN JOURNAL OF HUMAN GENETICS
Volume 80, Issue 3, Pages 561-566Publisher
CELL PRESS
DOI: 10.1086/512489
Keywords
-
Categories
Ask authors/readers for more resources
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.1564C -> 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available