Novel missense mutation in CLN8 in late infantile neuronal ceroid lipofuscinosis: The first report of a CLN8 mutation in Japan

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• 作者：Yu Katata^a ; Mitsugu Uematsu^a ; ^{uematsu@bk9.so-net.ne.jp" class="auth_mail" title="E-mail the corresponding author} ; Hiroki Sato^a ; Sato Suzuki^a ; Tojo Nakayama^a ; Yuki Kubota^a ; Tomoko Kobayashi^a ; Naomi Hino-Fukuyo^a ; Hirotomo Saitsu^b ; Shigeo Kure^a
• 关键词：Late infantile neuronal ceroid lipofuscinosis ; CLN8 ; Whole-exome sequence ; Progressive myoclonic epilepsy
• 刊名：Brain and Development
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：38
• 期：3
• 页码：341-345
• 全文大小：1329 K

文摘

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.