Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/22709
Title: Pathogenic Variants in CEP85L Cause Sporadic and Familial Posterior Predominant Lissencephaly.
Authors: Tsai, Meng-Han;Muir, Alison M;Wang, Won-Jing;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
Affiliation: Department of Pediatrics, University of Washington, Seattle, WA 98195, USA
Department of Pediatrics, University of Washington, Seattle, WA 98195, USA
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98105, USA
Murdoch Children's Research Institute, Royal Children's Hospital, Parkville 3052, Victoria, Australia
Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan 833, ROC
School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan 33302, ROC
Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan, ROC
Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan, ROC
Brotman Baty Institute for Precision Medicine, Seattle, WA, USA
Institute of Brain Science, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
Brain Research Center, National Yang-Ming University, Taipei 112, Taiwan, ROC
Department of Biological Science & Technology, National Chiao Tung University, Hsin-Chu 30010, Taiwan, ROC
Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Neurosciences Unit, Queensland Children's Hospital and School of Medicine, University of Queensland, Brisbane 4101, QLD, Australia
The Florey Institute of Neuroscience and Mental Health, Melbourne 3052, Victoria, Australia
Departments of Paediatrics and Neurology, The Royal Children's Hospital, The University of Melbourne, Melbourne 3052, Victoria, Australia
Institute of Biochemistry and Molecular Biology, College of Life Science, National Yang-Ming University, Taipei, Taiwan, ROC
Institute of Brain Science, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
Institute of Biochemistry and Molecular Biology, College of Life Science, National Yang-Ming University, Taipei, Taiwan, ROC
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC
Department of Neurology, Stanford University School of Medicine, Palo Alto, CA, USA
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
Department of Pediatrics, McGill University, Montreal, QC, Canada
Department of Paediatric Neurology, Hôpital Universitaire des Enfants Reine Fabiola, HUDERF, Université Libre de Bruxelles (ULB), Brussels, Belgium
Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan, ROC
Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan, ROC
Department of Pediatrics, University of Washington, Seattle, WA 98195, USA
Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
Division of Neurology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia
Issue Date: 10-Feb-2020
EDate: 2020-02-10
Citation: Neuron 2020; online first: 10 February
Abstract: 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/22709
DOI: 10.1016/j.neuron.2020.01.027
ORCID: 0000-0003-4580-841X
PubMed URL: 32097630
Type: Journal Article
Subjects: CEP85L
centrosome
lissencephaly
pachygyria
posterior predominant
subcortical band heterotopia
Appears in Collections:Journal articles

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