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	Kazuhiro Iwama, Masayuki Sasaki, Shinichi Hirabayashi, Chihiro Ohba, Emi Iwabuchi, Satoko Miyatake, Mitsuko Nakashima, Noriko Miyake, Shuichi Ito, Hirotomo Saitsu, Naomichi Matsumoto
Journal	Journal of human genetics (J Hum Genet) Vol. 61 Issue 6 Pg. 527-31 (Jun 2016) ISSN: 1435-232X [Electronic] England
PMID	26888482 (Publication Type: Journal Article)
Chemical References	Amino Acyl-tRNA Synthetases O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase, human
Topics	Adolescent Alleles Amino Acid Substitution Amino Acyl-tRNA Synthetases (genetics) Brain (cytology) Child Child, Preschool Exome Female Gene Frequency Genotype High-Throughput Nucleotide Sequencing Humans Infant Magnetic Resonance Imaging Male Mutation Olivopontocerebellar Atrophies (diagnosis, genetics) Pedigree Phenotype Polymorphism, Single Nucleotide Sequence Analysis, DNA

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