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Hum Mutat. 2015 Jan;36(1):106-17. doi: 10.1002/humu.22718.

Variants in CUL4B are associated with cerebral malformations.

Author information

1
Department of Human Genetics, Radboud Institute for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.

Abstract

Variants in cullin 4B (CUL4B) are a known cause of syndromic X-linked intellectual disability. Here, we describe an additional 25 patients from 11 families with variants in CUL4B. We identified nine different novel variants in these families and confirmed the pathogenicity of all nontruncating variants. Neuroimaging data, available for 15 patients, showed the presence of cerebral malformations in ten patients. The cerebral anomalies comprised malformations of cortical development (MCD), ventriculomegaly, and diminished white matter volume. The phenotypic heterogeneity of the cerebral malformations might result from the involvement of CUL-4B in various cellular pathways essential for normal brain development. Accordingly, we show that CUL-4B interacts with WDR62, a protein in which variants were previously identified in patients with microcephaly and a wide range of MCD. This interaction might contribute to the development of cerebral malformations in patients with variants in CUL4B.

KEYWORDS:

CUL4B; WDR62; cortical dysplasia; hydrocephalus; intellectual disability; mutation

PMID:
25385192
PMCID:
PMC4608231
DOI:
10.1002/humu.22718
[Indexed for MEDLINE]
Free PMC Article

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