| Literature DB >> 32097630 |
Meng-Han Tsai1, Alison M Muir2, Won-Jing Wang3, Yi-Ning Kang4, Kun-Chuan Yang4, Nian-Hsin Chao4, Mei-Feng Wu3, Ying-Chao Chang5, Brenda E Porter6, Laura A Jansen7, Guillaume Sebire8, Nicolas Deconinck9, Wen-Lang Fan10, Shih-Chi Su11, Wen-Hung Chung12, Edith P Almanza Fuerte2, Michele G Mehaffey2, Ching-Ching Ng13, Chung-Kin Chan13, Kheng-Seang Lim14, Richard J Leventer15, Paul J Lockhart15, Kate Riney16, John A Damiano17, Michael S Hildebrand17, Ghayda M Mirzaa18, William B Dobyns18, Samuel F Berkovic19, Ingrid E Scheffer20, Jin-Wu Tsai21, Heather C Mefford22.
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.Entities:
Keywords: CEP85L; centrosome; lissencephaly; pachygyria; posterior predominant; subcortical band heterotopia
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Year: 2020 PMID： 32097630 PMCID： PMC7357395 DOI： 10.1016/j.neuron.2020.01.027
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173