title: Single nucleotide variations in CLCN6 identified in patients with benign partial epilepsies in infancy and/or febrile seizures.
abstract: Nucleotide alterations in the gene encoding proline-rich transmembrane protein 2 (PRRT2) have been identified in most patients with benign partial epilepsies in infancy (BPEI)/benign familial infantile epilepsy (BFIE). However, not all patients harbor these PRRT2 mutations, indicating the involvement of genes other than PRRT2. In this study, we performed whole exome sequencing analysis for a large family affected with PRRT2-unrelated BPEI. We identified a non-synonymous single nucleotide variation (SNV) in the voltage-sensitive chloride channel 6 gene (CLCN6). A cohort study of 48 BPEI patients without PRRT2 mutations revealed a different CLCN6 SNV in a patient, his sibling and his father who had a history of febrile seizures (FS) but not BPEI. Another study of 48 patients with FS identified an additional SNV in CLCN6. Chloride channels (CLCs) are involved in a multitude of physiologic processes and some members of the CLC family have been linked to inherited diseases. However, a phenotypic correlation has not been confirmed for CLCN6. Although we could not detect significant biological effects linked to the identified CLCN6 SNVs, further studies should investigate potential CLCN6 variants that may underlie the genetic susceptibility to convulsive disorders.
authors: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors: Toshiyuki
authors: T
authors: Yamamoto
authors: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors: Keiko
authors: K
authors: Shimojima
authors: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors: Noriko
authors: N
authors: Sangu
authors: Department of Hygiene and Public Health I, Tokyo Women's Medical University, Tokyo, Japan.
authors: Yuta
authors: Y
authors: Komoike
authors: Department of Pediatrics, Fukuoka University Faculty of Medicine, Fukuoka, Japan.
authors: Atsushi
authors: A
authors: Ishii
authors: Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors: Shinpei
authors: S
authors: Abe
authors: Department of Pediatrics, Juntendo Nerima Hospital, Tokyo, Japan.
authors: Shintaro
authors: S
authors: Yamashita
authors: National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
authors: Katsumi
authors: K
authors: Imai
authors: Department of Pediatrics, Anjo Kosei Hospital, Anjo, Japan.
authors: Tetsuo
authors: T
authors: Kubota
authors: Department of Pediatrics, Anjo Kosei Hospital, Anjo, Japan.
authors: Tatsuya
authors: T
authors: Fukasawa
authors: Department of Child Neurology, Seirei Hamamatsu General Hospital, Hamamatsu, Japan.
authors: Tohru
authors: T
authors: Okanishi
authors: Department of Child Neurology, Seirei Hamamatsu General Hospital, Hamamatsu, Japan.
authors: Hideo
authors: H
authors: Enoki
authors: Tanabe Monbayashi Child Clinic, Hirakata, Japan.
authors: Takuya
authors: T
authors: Tanabe
authors: StaGen Co., Ltd., Tokyo, Japan.
authors: Akira
authors: A
authors: Saito
authors: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors: Toru
authors: T
authors: Furukawa
authors: Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors: Toshiaki
authors: T
authors: Shimizu
authors: Florey Neuroscience Institute, Melbourne Brain Centre, The University of Melbourne, Melbourne, Victoria, Australia.
authors: Carol J
authors: CJ
authors: Milligan
authors: Florey Neuroscience Institute, Melbourne Brain Centre, The University of Melbourne, Melbourne, Victoria, Australia.
authors: Steven
authors: S
authors: Petrou
authors: Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors: Sarah E
authors: SE
authors: Heron
authors: Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors: Leanne M
authors: LM
authors: Dibbens
authors: Department of Pediatrics, Fukuoka University Faculty of Medicine, Fukuoka, Japan.
authors: Shinichi
authors: S
authors: Hirose
authors: Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors: Akihisa
authors: A
authors: Okumura
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D018118:Chloride Channels / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D020936:Epilepsy, Benign Neonatal / Q000150:complications* / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D003294:Seizures, Febrile / Q000150:complications* / Q000235:genetics*
chemical_list: C097539:CLCN6 protein, human; D018118:Chloride Channels; D012333:RNA, Messenger