TY - JOUR
T1 - Novel missense mutation in CLN8 in late infantile neuronal ceroid lipofuscinosis
T2 - The first report of a CLN8 mutation in Japan
AU - Katata, Yu
AU - Uematsu, Mitsugu
AU - Sato, Hiroki
AU - Suzuki, Sato
AU - Nakayama, Tojo
AU - Kubota, Yuki
AU - Kobayashi, Tomoko
AU - Fukuyo, Naomi
AU - Saitsu, Hirotomo
AU - Kure, Shigeo
N1 - Publisher Copyright:
© 2015 The Japanese Society of Child Neurology.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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 3 years, 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.
AB - 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 3 years, 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.
KW - CLN8
KW - Late infantile neuronal ceroid lipofuscinosis
KW - Progressive myoclonic epilepsy
KW - Whole-exome sequence
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U2 - 10.1016/j.braindev.2015.09.008
DO - 10.1016/j.braindev.2015.09.008
M3 - Article
C2 - 26443629
AN - SCOPUS:84958102750
VL - 38
SP - 341
EP - 345
JO - Brain and Development
JF - Brain and Development
SN - 0387-7604
IS - 3
ER -