title: Exome sequencing identifies SUCO mutations in mesial temporal lobe epilepsy.
abstract: Mesial temporal lobe epilepsy (mTLE) is the main type and most common medically intractable form of epilepsy. Severity of disease-based stratified samples may help identify new disease-associated mutant genes. We analyzed mRNA expression profiles from patient hippocampal tissue. Three of the seven patients had severe mTLE with generalized-onset convulsions and consciousness loss that occurred over many years. We found that compared with other groups, patients with severe mTLE were classified into a distinct group. Whole-exome sequencing and Sanger sequencing validation in all seven patients identified three novel SUN domain-containing ossification factor (SUCO) mutations in severely affected patients. Furthermore, SUCO knock down significantly reduced dendritic length in vitro. Our results indicate that mTLE defects may affect neuronal development, and suggest that neurons have abnormal development due to lack of SUCO, which may be a generalized-onset epilepsy-related gene.
authors: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing 10005, China.
authors: Zhiqiang
authors: Z
authors: Sha
authors: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing 10005, China.
authors: Longze
authors: L
authors: Sha
authors: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing 10005, China.
authors: Wenting
authors: W
authors: Li
authors: Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, China.
authors: Wanchen
authors: W
authors: Dou
authors: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing 10005, China.
authors: Yan
authors: Y
authors: Shen
authors: Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, China. Electronic address: wlw1946@yahoo.com.cn.
authors: Liwen
authors: L
authors: Wu
authors: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing 10005, China. Electronic address: xuqi@pumc.edu.cn.
authors: Qi
authors: Q
authors: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D016022:Case-Control Studies; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003712:Dendrites / Q000648:ultrastructure; D004833:Epilepsy, Temporal Lobe / Q000235:genetics* / Q000378:metabolism; D059472:Exome; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C404748:SUCO protein, human; C550250:osteopotentia protein, mouse
keywords: Dendritic formation; Mesial temporal lobe epilepsy; Whole-exome sequencing