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Variants in CUL4B are associated with cerebral malformations.

Authors :: Vulto-van Silfhout AT
Nakagawa T
Bahi-Buisson N
Haas SA
Hu H
Bienek M
Vissers LE
Gilissen C
Tzschach A
Busche A
Müsebeck J
Rump P
Mathijssen IB
Avela K
Somer M
Doagu F
Philips AK
Rauch A
Baumer A
Voesenek K
Poirier K
Vigneron J
Amram D
Odent S
Nawara M
Obersztyn E
Lenart J
Charzewska A
Lebrun N
Fischer U
Nillesen WM
Yntema HG
Järvelä I
Ropers HH
de Vries BB
Brunner HG
van Bokhoven H
Raymond FL
Willemsen MA
Chelly J
Xiong Y
Barkovich AJ
Kalscheuer VM
Kleefstra T
de Brouwer AP
Source :: Human mutation [Hum Mutat] 2015 Jan; Vol. 36 (1), pp. 106-17.
Publication Year :: 2015
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.<br /> (© 2014 WILEY PERIODICALS, INC.)