Variants in CUL4B are Associated with Cerebral Malformations

Anneke T. Vulto-van Silfhout; Tadashi Nakagawa; Nadia Bahi-Buisson; Stefan A. Haas; Hao Hu; Melanie Bienek; Lisenka E. L. M. Vissers; Christian Gilissen; Andreas Tzschach; Andreas Busche; Jörg Müsebeck; Patrick Rump; Inge B. Mathijssen; Kristiina Avela; Mirja Somer; Fatma Doagu; Anju K. Philips; Anita Rauch; Alessandra Baumer; Krysta Voesenek; Karine Poirier; Jacqueline Vigneron; Daniel Amram; Sylvie Odent; Magdalena Nawara; Ewa Obersztyn; Jacek Lenart; Agnieszka Charzewska; Nicolas Lebrun; Ute Fischer; Willy M. Nillesen; Helger G. Yntema; Irma Järvelä; Hans-Hilger Ropers; Bert B. A. de Vries; Han G. Brunner; Hans van Bokhoven; F. Lucy Raymond; Michèl A. A. P. Willemsen; Jamel Chelly; Yue Xiong; A. James Barkovich; Vera M. Kalscheuer; Tjitske Kleefstra; Arjan P. M. de Brouwer

doi:https://doi.org/10.1002/humu.22718

Variants in CUL4B are Associated with Cerebral Malformations

Anneke T. Vulto-van Silfhout, Tadashi Nakagawa, Nadia Bahi-Buisson, Stefan A. Haas, Hao Hu, Melanie Bienek, Lisenka E. L. M. Vissers, Christian Gilissen, Andreas Tzschach, Andreas Busche, Jörg Müsebeck, Patrick Rump, Inge B. Mathijssen, Kristiina Avela, Mirja Somer, Fatma Doagu, Anju K. Philips, Anita Rauch, Alessandra Baumer, Krysta VoesenekKarine Poirier, Jacqueline Vigneron, Daniel Amram, Sylvie Odent, Magdalena Nawara, Ewa Obersztyn, Jacek Lenart, Agnieszka Charzewska, Nicolas Lebrun, Ute Fischer, Willy M. Nillesen, Helger G. Yntema, Irma Järvelä, Hans-Hilger Ropers, Bert B. A. de Vries, Han G. Brunner, Hans van Bokhoven, F. Lucy Raymond, Michèl A. A. P. Willemsen, Jamel Chelly, Yue Xiong, A. James Barkovich, Vera M. Kalscheuer, Tjitske Kleefstra, Arjan P. M. de Brouwer

Human Genetics (AMC)

Research output: Contribution to journal › Article › Academic › peer-review

37 Citations (Scopus)

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

Original language	English
Pages (from-to)	106-117
Journal	Human mutation
Volume	36
Issue number	1
DOIs	https://doi.org/10.1002/humu.22718
Publication status	Published - 2015

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https://doi.org/10.1002/humu.22718

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Vulto-van Silfhout, A. T., Nakagawa, T., Bahi-Buisson, N., Haas, S. A., Hu, H., Bienek, M., Vissers, L. E. L. M., Gilissen, C., Tzschach, A., Busche, A., Müsebeck, J., Rump, P., Mathijssen, I. B., Avela, K., Somer, M., Doagu, F., Philips, A. K., Rauch, A., Baumer, A., ... de Brouwer, A. P. M. (2015). Variants in CUL4B are Associated with Cerebral Malformations. Human mutation, 36(1), 106-117. https://doi.org/10.1002/humu.22718

@article{17bc2c40eb0c4a30b848aff71d9e6847,

title = "Variants in CUL4B are Associated with Cerebral Malformations",

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",

author = "{Vulto-van Silfhout}, {Anneke T.} and Tadashi Nakagawa and Nadia Bahi-Buisson and Haas, {Stefan A.} and Hao Hu and Melanie Bienek and Vissers, {Lisenka E. L. M.} and Christian Gilissen and Andreas Tzschach and Andreas Busche and J{\"o}rg M{\"u}sebeck and Patrick Rump and Mathijssen, {Inge B.} and Kristiina Avela and Mirja Somer and Fatma Doagu and Philips, {Anju K.} and Anita Rauch and Alessandra Baumer and Krysta Voesenek and Karine Poirier and Jacqueline Vigneron and Daniel Amram and Sylvie Odent and Magdalena Nawara and Ewa Obersztyn and Jacek Lenart and Agnieszka Charzewska and Nicolas Lebrun and Ute Fischer and Nillesen, {Willy M.} and Yntema, {Helger G.} and Irma J{\"a}rvel{\"a} and Hans-Hilger Ropers and {de Vries}, {Bert B. A.} and Brunner, {Han G.} and {van Bokhoven}, Hans and Raymond, {F. Lucy} and Willemsen, {Mich{\`e}l A. A. P.} and Jamel Chelly and Yue Xiong and Barkovich, {A. James} and Kalscheuer, {Vera M.} and Tjitske Kleefstra and {de Brouwer}, {Arjan P. M.}",

year = "2015",

doi = "https://doi.org/10.1002/humu.22718",

language = "English",

volume = "36",

pages = "106--117",

journal = "Human mutation",

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Vulto-van Silfhout, AT, Nakagawa, T, Bahi-Buisson, N, Haas, SA, Hu, H, Bienek, M, Vissers, LELM, 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, H-H, de Vries, BBA, Brunner, HG, van Bokhoven, H, Raymond, FL, Willemsen, MAAP, Chelly, J, Xiong, Y, Barkovich, AJ, Kalscheuer, VM, Kleefstra, T & de Brouwer, APM 2015, 'Variants in CUL4B are Associated with Cerebral Malformations', Human mutation, vol. 36, no. 1, pp. 106-117. https://doi.org/10.1002/humu.22718

TY - JOUR

T1 - Variants in CUL4B are Associated with Cerebral Malformations

AU - Vulto-van Silfhout, Anneke T.

AU - Nakagawa, Tadashi

AU - Bahi-Buisson, Nadia

AU - Haas, Stefan A.

AU - Hu, Hao

AU - Bienek, Melanie

AU - Vissers, Lisenka E. L. M.

AU - Gilissen, Christian

AU - Tzschach, Andreas

AU - Busche, Andreas

AU - Müsebeck, Jörg

AU - Rump, Patrick

AU - Mathijssen, Inge B.

AU - Avela, Kristiina

AU - Somer, Mirja

AU - Doagu, Fatma

AU - Philips, Anju K.

AU - Rauch, Anita

AU - Baumer, Alessandra

AU - Voesenek, Krysta

AU - Poirier, Karine

AU - Vigneron, Jacqueline

AU - Amram, Daniel

AU - Odent, Sylvie

AU - Nawara, Magdalena

AU - Obersztyn, Ewa

AU - Lenart, Jacek

AU - Charzewska, Agnieszka

AU - Lebrun, Nicolas

AU - Fischer, Ute

AU - Nillesen, Willy M.

AU - Yntema, Helger G.

AU - Järvelä, Irma

AU - Ropers, Hans-Hilger

AU - de Vries, Bert B. A.

AU - Brunner, Han G.

AU - van Bokhoven, Hans

AU - Raymond, F. Lucy

AU - Willemsen, Michèl A. A. P.

AU - Chelly, Jamel

AU - Xiong, Yue

AU - Barkovich, A. James

AU - Kalscheuer, Vera M.

AU - Kleefstra, Tjitske

AU - de Brouwer, Arjan P. M.

PY - 2015

Y1 - 2015

N2 - 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

AB - 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

U2 - https://doi.org/10.1002/humu.22718

DO - https://doi.org/10.1002/humu.22718

M3 - Article

C2 - 25385192

SN - 1059-7794

VL - 36

SP - 106

EP - 117

JO - Human mutation

JF - Human mutation

IS - 1

ER -