title: Novel missense mutation in CLN8 in late infantile neuronal ceroid lipofuscinosis: The first report of a CLN8 mutation in Japan.
abstract: Neuronal ceroid lipofuscinoses (NCLs) are clinically and genetically heterogeneous neurodegenerative lysosomal diseases. Fourteen distinct NCL subtypes (CLN1-CLN14) are known, and they are caused by mutations in different genes. CLN8 was first identified in Finnish patients, and the phenotype was subsequently found in Turkish, Italian, and Pakistani patients. We report a 6-year-old Japanese boy with NCL with a novel missense mutation in CLN8. At the age of 3years, he manifested frequent drop seizures, and then progressively developed motor difficulties with an ataxic gait, myoclonus, left conjugate deviation, and rotational nystagmus. At age 5, he developed profound visual difficulty and dysphagia, and he has now lost his mobility. A bone marrow examination at age 5 showed sea-blue histiocytes. An electroretinogram was non-recordable. No giant somatosensory evoked potentials were found. Brain magnetic resonance imaging revealed bilateral diffuse hyperintensities in the white matter around the lateral ventricles and cerebellar and pontine atrophy on T2-weighted images. In a lysosomal enzyme study, the palmitoyl-protein-thioesterase and pepinase activity was within normal limits. Whole-exome sequencing revealed a homozygous CLN8 mutation: c.620T>G (p.L207R). His parents were both heterozygous for this mutation. To our knowledge, this is the first report of a CLN8 mutation in late infantile NCL in Japan.
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Katata
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan. Electronic address: uematsu@bk9.so-net.ne.jp.
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Uematsu
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Sato
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Tojo
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kubota
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Hino-Fukuyo
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
mesh_terms: D002648:Child; D004831:Epilepsies, Myoclonic / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA
chemical_list: C121767:CLN8 protein, human; D008565:Membrane Proteins
keywords: CLN8; Late infantile neuronal ceroid lipofuscinosis; Progressive myoclonic epilepsy; Whole-exome sequence