title: FARS2 mutation and epilepsy: Possible link with early-onset epileptic encephalopathy.
abstract: Early-onset epileptic encephalopathy (EOEE) consists of a heterogeneous group of epilepsy phenotypes. Recent technological advances in molecular biology have also rapidly expanded the genotype of EOEE. Genes involved in diverse molecular pathways, including ion channels, synaptic structure, transcription regulation, and cellular growth, have been implicated in EOEE. Mitochondrial aminoacyl tRNA synthetase, which plays a key role in mitochondrial protein synthesis by attaching 20 different amino acids to the tRNA tail, has been recently linked with the epilepsy phenotype. Here, we report a novel homozygous c.925G>A (G309S) missense mutation in the gene that encodes the human mitochondrial phenylalanyl-tRNA synthetase (FARS2) in four patients from two nonconsanguineous Korean families. All four patients suffered from intractable seizures that started at the age of 3 and 4 months. Seizure types were variable, including infantile spasms and myoclonic seizures, and often prolonged. Although their initial development seemed to be normal, relentless regression after seizure onset occurred in all patients. An etiologic investigation, including brain imaging and metabolic studies, did not reveal a specific etiology. We reviewed the epilepsy phenotypes of six additional FARS2 mutation-positive patients and suggest that FARS2 can be considered one of the genetic causes of EOEE.
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Jongro-Gu, Daehak-ro 101, Seoul, Republic of Korea. Electronic address: gipumj@gmail.com.
authors.forename: Jae So
authors.initials: JS
authors.lastname: Cho
authors.affiliation: Department of Pediatrics, Jeju National University Hospital 753-3, Arail-dong, Jeju-si, Jeju-do, Republic of Korea. Electronic address: aquack@hanmail.net.
authors.forename: Seung Hyo
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Applied Physics and Applied Mathematics, School of Engineering and Applied Science, Columbia University, New York, NY, USA. Electronic address: ha01994@naver.com.
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Korea Advanced Institute of Science and Technology, Yusung-Gu, Daehak-ro 291, Daejun City, Republic of Korea. Electronic address: hibissyria@gmail.com.
authors.forename: Taesu
authors.initials: T
authors.lastname: Chung
authors.affiliation: Korea Advanced Institute of Science and Technology, Yusung-Gu, Daehak-ro 291, Daejun City, Republic of Korea. Electronic address: kds@kaist.ac.kr.
authors.forename: Dongsup
authors.initials: D
authors.lastname: Kim
authors.affiliation: Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Republic of Korea. Electronic address: ja_sesong_ng@hotmail.com.
authors.forename: Sesong
authors.initials: S
authors.lastname: Jang
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Jongro-Gu, Daehak-ro 101, Seoul, Republic of Korea. Electronic address: for3guy@naver.com.
authors.forename: Seung Bok
authors.initials: SB
authors.lastname: Lee
authors.affiliation: Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Republic of Korea. Electronic address: ysk819@daum.net.
authors.forename: Seung Keun
authors.initials: SK
authors.lastname: Yoo
authors.affiliation: Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Republic of Korea. Electronic address: jongyeon.anna@gmail.com.
authors.forename: Jongyeon
authors.initials: J
authors.lastname: Shin
authors.affiliation: Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Republic of Korea. Electronic address: jongil@snu.ac.kr.
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Seoul National University Bundang Hospital, Bundang-Gu, Gumi-ro 173-82, Sungnam City, Gyunggi-do, Republic of Korea. Electronic address: hunminkim@hanmail.net.
authors.forename: Hunmin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Seoul National University Bundang Hospital, Bundang-Gu, Gumi-ro 173-82, Sungnam City, Gyunggi-do, Republic of Korea. Electronic address: seizure@snu.ac.kr.
authors.forename: Hee
authors.initials: H
authors.lastname: Hwang
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Jongro-Gu, Daehak-ro 101, Seoul, Republic of Korea. Electronic address: chaeped1@snu.ac.kr.
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Chae
authors.affiliation: Department of Pediatrics, Seoul National University Boramae Hospital, Dogjak-gu, Borame-ro 5-20, Seoul, Republic of Korea. Electronic address: jechoi66@snu.ac.kr.
authors.forename: Jieun
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Jongro-Gu, Daehak-ro 101, Seoul, Republic of Korea. Electronic address: pednr@plaza.snu.ac.kr.
authors.forename: Ki Joong
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Jongro-Gu, Daehak-ro 101, Seoul, Republic of Korea. Electronic address: prabbit7@snu.ac.kr.
authors.forename: Byung Chan
authors.initials: BC
authors.lastname: Lim
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging; D004827:Epilepsy / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D020125:Mutation, Missense; D010641:Phenotype; D010652:Phenylalanine-tRNA Ligase / Q000235:genetics* / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; C000611567:FARS2 protein, human; D010652:Phenylalanine-tRNA Ligase
keywords: Early-onset epileptic encephalopathy; FARS2; Mitochondrial tRNA synthetase