Variants in CUL4B are associated with cerebral malformations.
Variants in CUL4B are associated with cerebral malformations.
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DOI：
10.1002/humu.22718
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发表时间：
2015-01
期刊：
影响因子：
3.9
通讯作者：
de Brouwer AP
中科院分区：
文献类型：
--
作者：
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
cullin 4B (CUL4B) 的变异体是导致 X 连锁智力障碍综合征的已知原因。在这里，我们描述了来自 11 个家庭的另外 25 名患有 CUL4B 变异的患者。我们在这些家族中鉴定了九种不同的新变异，并证实了所有非截短变异的致病性。 15 名患者的神经影像数据显示，10 名患者存在脑畸形。大脑异常包括皮质发育畸形（MCD）、脑室扩大和白质体积减少。脑畸形的表型异质性可能是由于 CUL-4B 参与正常大脑发育所必需的各种细胞途径所致。因此，我们发现 CUL-4B 与 WDR62 相互作用，WDR62 是一种蛋白质，之前在小头畸形和多种 MCD 患者中发现了该蛋白质的变异体。这种相互作用可能导致 CUL4B 变异患者发生脑畸形。
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.