title: Milder progressive cerebellar atrophy caused by biallelic SEPSECS mutations.
abstract: Cerebellar atrophy is recognized in various types of childhood neurological disorders with clinical and genetic heterogeneity. Genetic analyses such as whole exome sequencing are useful for elucidating the genetic basis of these conditions. Pathological recessive mutations in Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase (SEPSECS) have been reported in a total of 11 patients with pontocerebellar hypoplasia type 2, progressive cerebellocerebral atrophy or progressive encephalopathy, yet detailed clinical features are limited to only four patients. We identified two new families with progressive cerebellar atrophy, and by whole exome sequencing detected biallelic SEPSECS mutations: c.356A>G (p.Asn119Ser) and c.77delG (p.Arg26Profs*42) in family 1, and c.356A>G (p.Asn119Ser) and c.467G>A (p.Arg156Gln) in family 2. Their development was slightly delayed regardless of normal brain magnetic resonance imaging (MRI) in infancy. The progression of clinical symptoms in these families is evidently slower than in previously reported cases, and the cerebellar atrophy milder by brain MRI, indicating that SEPSECS mutations are also involved in milder late-onset cerebellar atrophy.
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.|Department of Pediatrics, Yokohama City University, Yokohama, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Iwama
authors.affiliation: Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Division of Neurology, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirabayashi
authors.affiliation: Department of Clinical Neurology and Stroke Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Ohba
authors.affiliation: Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Iwabuchi
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Miyatake
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Department of Pediatrics, Yokohama City University, Yokohama, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Hirotomo
authors.identifier: http://orcid.org/0000-0003-0723-0960
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D000293:Adolescent; D000483:Alleles; D019943:Amino Acid Substitution; D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics*; D001921:Brain / Q000166:cytology; D002648:Child; D002675:Child, Preschool; D059472:Exome; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009849:Olivopontocerebellar Atrophies / Q000175:diagnosis* / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D000604:Amino Acyl-tRNA Synthetases; C542370:O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase, human