Variants in CUL4B are associated with cerebral malformations.
Hum Mutat
; 36(1): 106-17, 2015 Jan.
Article
in En
| MEDLINE
| ID: mdl-25385192
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
/
Mental Retardation, X-Linked
/
Cullin Proteins
/
Malformations of Cortical Development
/
Nerve Tissue Proteins
Type of study:
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Humans
/
Infant
/
Male
/
Middle aged
Language:
En
Journal:
Hum Mutat
Journal subject:
GENETICA MEDICA
Year:
2015
Type:
Article
Affiliation country:
Netherlands