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Pathogenic Variants in CEP85L Cause Sporadic and Familial Posterior Predominant Lissencephaly

Lissencephaly (LIS), denoting a “smooth brain,” is characterized by the absence of normal cerebral convolutions with abnormalities of cortical thickness. Pathogenic variants in over 20 genes are associated with LIS. The majority of posterior predominant LIS is caused by pathogenic variants in LIS1 (...

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Main Authors: Tsai, Meng Han, Muir, Alison M., Wang, Won nJing, Kang, Yi Ning, Yang, Kun Chuan, Chao, Nian Hsin, Wu, Mei Feng, Chang, Ying Chao, Porter, Brenda E., Jansen, Laura A., Sebire, Guillaume, Deconinck, Nicolas, Fan, Wen Lang, Su, Shih Chi, Chung, Wen Hung, Almanza Fuerte, Edith P., Mehaffey, Michele G., Ng, Ching Ching, Chan, Chung Kin, Lim, Kheng Seang, Leventer, Richard J., Lockhart, Paul J., Riney, Kate, Damiano, John A., Hildebrand, Michael S., Mirzaa, Ghayda M., Dobyns, William B., Berkovic, Samuel F., Scheffer, Ingrid E., Tsai, Jin Wu, Mefford, Heather C.
Format: Article
Published: Elsevier 2020
Subjects:
QH Natural history
R Medicine
Online Access:http://eprints.um.edu.my/24797/
https://doi.org/10.1016/j.neuron.2020.01.027
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spelling my.um.eprints.247972020-06-11T03:59:39Z http://eprints.um.edu.my/24797/ Pathogenic Variants in CEP85L Cause Sporadic and Familial Posterior Predominant Lissencephaly Tsai, Meng Han Muir, Alison M. Wang, Won nJing Kang, Yi Ning Yang, Kun Chuan Chao, Nian Hsin Wu, Mei Feng Chang, Ying Chao Porter, Brenda E. Jansen, Laura A. Sebire, Guillaume Deconinck, Nicolas Fan, Wen Lang Su, Shih Chi Chung, Wen Hung Almanza Fuerte, Edith P. Mehaffey, Michele G. Ng, Ching Ching Chan, Chung Kin Lim, Kheng Seang Leventer, Richard J. Lockhart, Paul J. Riney, Kate Damiano, John A. Hildebrand, Michael S. Mirzaa, Ghayda M. Dobyns, William B. Berkovic, Samuel F. Scheffer, Ingrid E. Tsai, Jin Wu Mefford, Heather C. QH Natural history R Medicine Lissencephaly (LIS), denoting a “smooth brain,” is characterized by the absence of normal cerebral convolutions with abnormalities of cortical thickness. Pathogenic variants in over 20 genes are associated with LIS. The majority of posterior predominant LIS is caused by pathogenic variants in LIS1 (also known as PAFAH1B1), although a significant fraction remains without a known genetic etiology. We now implicate CEP85L as an important cause of posterior predominant LIS, identifying 13 individuals with rare, heterozygous CEP85L variants, including 2 families with autosomal dominant inheritance. We show that CEP85L is a centrosome protein localizing to the pericentriolar material, and knockdown of Cep85l causes a neuronal migration defect in mice. LIS1 also localizes to the centrosome, suggesting that this organelle is key to the mechanism of posterior predominant LIS. © 2020 Elsevier Inc. Tsai et al. implicate CEP85L as an important cause of posterior predominant lissencephaly, identifying 13 individuals with rare, heterozygous CEP85L variants, including 2 families with autosomal dominant inheritance. © 2020 Elsevier Inc. Elsevier 2020 Article PeerReviewed Tsai, Meng Han and Muir, Alison M. and Wang, Won nJing and Kang, Yi Ning and Yang, Kun Chuan and Chao, Nian Hsin and Wu, Mei Feng and Chang, Ying Chao and Porter, Brenda E. and Jansen, Laura A. and Sebire, Guillaume and Deconinck, Nicolas and Fan, Wen Lang and Su, Shih Chi and Chung, Wen Hung and Almanza Fuerte, Edith P. and Mehaffey, Michele G. and Ng, Ching Ching and Chan, Chung Kin and Lim, Kheng Seang and Leventer, Richard J. and Lockhart, Paul J. and Riney, Kate and Damiano, John A. and Hildebrand, Michael S. and Mirzaa, Ghayda M. and Dobyns, William B. and Berkovic, Samuel F. and Scheffer, Ingrid E. and Tsai, Jin Wu and Mefford, Heather C. (2020) Pathogenic Variants in CEP85L Cause Sporadic and Familial Posterior Predominant Lissencephaly. Neuron, 106 (2). 237-245.e8. ISSN 0896-6273 https://doi.org/10.1016/j.neuron.2020.01.027 doi:10.1016/j.neuron.2020.01.027
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic QH Natural history
R Medicine
spellingShingle QH Natural history
R Medicine
Tsai, Meng Han
Muir, Alison M.
Wang, Won nJing
Kang, Yi Ning
Yang, Kun Chuan
Chao, Nian Hsin
Wu, Mei Feng
Chang, Ying Chao
Porter, Brenda E.
Jansen, Laura A.
Sebire, Guillaume
Deconinck, Nicolas
Fan, Wen Lang
Su, Shih Chi
Chung, Wen Hung
Almanza Fuerte, Edith P.
Mehaffey, Michele G.
Ng, Ching Ching
Chan, Chung Kin
Lim, Kheng Seang
Leventer, Richard J.
Lockhart, Paul J.
Riney, Kate
Damiano, John A.
Hildebrand, Michael S.
Mirzaa, Ghayda M.
Dobyns, William B.
Berkovic, Samuel F.
Scheffer, Ingrid E.
Tsai, Jin Wu
Mefford, Heather C.
Pathogenic Variants in CEP85L Cause Sporadic and Familial Posterior Predominant Lissencephaly
description Lissencephaly (LIS), denoting a “smooth brain,” is characterized by the absence of normal cerebral convolutions with abnormalities of cortical thickness. Pathogenic variants in over 20 genes are associated with LIS. The majority of posterior predominant LIS is caused by pathogenic variants in LIS1 (also known as PAFAH1B1), although a significant fraction remains without a known genetic etiology. We now implicate CEP85L as an important cause of posterior predominant LIS, identifying 13 individuals with rare, heterozygous CEP85L variants, including 2 families with autosomal dominant inheritance. We show that CEP85L is a centrosome protein localizing to the pericentriolar material, and knockdown of Cep85l causes a neuronal migration defect in mice. LIS1 also localizes to the centrosome, suggesting that this organelle is key to the mechanism of posterior predominant LIS. © 2020 Elsevier Inc. Tsai et al. implicate CEP85L as an important cause of posterior predominant lissencephaly, identifying 13 individuals with rare, heterozygous CEP85L variants, including 2 families with autosomal dominant inheritance. © 2020 Elsevier Inc.
format Article
author Tsai, Meng Han
Muir, Alison M.
Wang, Won nJing
Kang, Yi Ning
Yang, Kun Chuan
Chao, Nian Hsin
Wu, Mei Feng
Chang, Ying Chao
Porter, Brenda E.
Jansen, Laura A.
Sebire, Guillaume
Deconinck, Nicolas
Fan, Wen Lang
Su, Shih Chi
Chung, Wen Hung
Almanza Fuerte, Edith P.
Mehaffey, Michele G.
Ng, Ching Ching
Chan, Chung Kin
Lim, Kheng Seang
Leventer, Richard J.
Lockhart, Paul J.
Riney, Kate
Damiano, John A.
Hildebrand, Michael S.
Mirzaa, Ghayda M.
Dobyns, William B.
Berkovic, Samuel F.
Scheffer, Ingrid E.
Tsai, Jin Wu
Mefford, Heather C.
author_facet Tsai, Meng Han
Muir, Alison M.
Wang, Won nJing
Kang, Yi Ning
Yang, Kun Chuan
Chao, Nian Hsin
Wu, Mei Feng
Chang, Ying Chao
Porter, Brenda E.
Jansen, Laura A.
Sebire, Guillaume
Deconinck, Nicolas
Fan, Wen Lang
Su, Shih Chi
Chung, Wen Hung
Almanza Fuerte, Edith P.
Mehaffey, Michele G.
Ng, Ching Ching
Chan, Chung Kin
Lim, Kheng Seang
Leventer, Richard J.
Lockhart, Paul J.
Riney, Kate
Damiano, John A.
Hildebrand, Michael S.
Mirzaa, Ghayda M.
Dobyns, William B.
Berkovic, Samuel F.
Scheffer, Ingrid E.
Tsai, Jin Wu
Mefford, Heather C.
author_sort Tsai, Meng Han
title Pathogenic Variants in CEP85L Cause Sporadic and Familial Posterior Predominant Lissencephaly
title_short Pathogenic Variants in CEP85L Cause Sporadic and Familial Posterior Predominant Lissencephaly
title_full Pathogenic Variants in CEP85L Cause Sporadic and Familial Posterior Predominant Lissencephaly
title_fullStr Pathogenic Variants in CEP85L Cause Sporadic and Familial Posterior Predominant Lissencephaly
title_full_unstemmed Pathogenic Variants in CEP85L Cause Sporadic and Familial Posterior Predominant Lissencephaly
title_sort pathogenic variants in cep85l cause sporadic and familial posterior predominant lissencephaly
publisher Elsevier
publishDate 2020
url http://eprints.um.edu.my/24797/
https://doi.org/10.1016/j.neuron.2020.01.027
_version_ 1674066730285006848
score 13.211869

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