CUL4B基因的变异与脑畸形有关。
Variants in CUL4B are associated with cerebral malformations.
作者信息
Vulto-van Silfhout Anneke T, Nakagawa Tadashi, Bahi-Buisson Nadia, Haas Stefan A, Hu Hao, Bienek Melanie, Vissers Lisenka E L M, Gilissen Christian, Tzschach Andreas, Busche Andreas, Müsebeck Jörg, Rump Patrick, Mathijssen Inge B, Avela Kristiina, Somer Mirja, Doagu Fatma, Philips Anju K, Rauch Anita, Baumer Alessandra, Voesenek Krysta, Poirier Karine, Vigneron Jacqueline, Amram Daniel, Odent Sylvie, Nawara Magdalena, Obersztyn Ewa, Lenart Jacek, Charzewska Agnieszka, Lebrun Nicolas, Fischer Ute, Nillesen Willy M, Yntema Helger G, Järvelä Irma, Ropers Hans-Hilger, de Vries Bert B A, Brunner Han G, van Bokhoven Hans, Raymond F Lucy, Willemsen Michèl A A P, Chelly Jamel, Xiong Yue, Barkovich A James, Kalscheuer Vera M, Kleefstra Tjitske, de Brouwer Arjan P M
机构信息
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.
出版信息
Hum Mutat. 2015 Jan;36(1):106-17. doi: 10.1002/humu.22718.
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.
泛素连接酶E3组分4B（CUL4B）基因变异是X连锁综合征型智力障碍的一个已知病因。在此，我们描述了另外25例来自11个家庭的CUL4B基因变异患者。我们在这些家庭中鉴定出9种不同的新变异，并证实了所有非截断变异的致病性。15例患者的神经影像学数据显示，其中10例存在脑畸形。脑异常包括皮质发育畸形（MCD）、脑室扩大和白质体积减小。脑畸形的表型异质性可能是由于CUL-4B参与了正常脑发育所必需的各种细胞途径。因此，我们发现CUL-4B与WDR62相互作用，WDR62是一种蛋白质，此前在小头畸形和多种MCD患者中发现了其变异。这种相互作用可能导致CUL4B基因变异患者脑畸形的发生。
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