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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Elsevier
2020
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| 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 |
| collection | UM |
| 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. |
| first_indexed | 2024-03-06T06:03:47Z |
| format | Article |
| id | um.eprints-24797 |
| institution | Universiti Malaya |
| last_indexed | 2024-03-06T06:03:47Z |
| publishDate | 2020 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | 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, DOI https://doi.org/10.1016/j.neuron.2020.01.027 <https://doi.org/10.1016/j.neuron.2020.01.027>. https://doi.org/10.1016/j.neuron.2020.01.027 doi:10.1016/j.neuron.2020.01.027 |
| 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 |
| title | 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_short | Pathogenic Variants in CEP85L Cause Sporadic and Familial Posterior Predominant Lissencephaly |
| title_sort | pathogenic variants in cep85l cause sporadic and familial posterior predominant lissencephaly |
| topic | QH Natural history R Medicine |
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