Rapid progression of a walking disability in a 5-year-old boy with a CLN6 mutation
Rapid progression of a walking disability in a 5-year-old boy with a CLN6 mutation
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DOI：
10.1016/j.braindev.2019.04.009
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发表时间：
2019-09-01
影响因子：
1.7
通讯作者：
Osaka, Hitoshi
中科院分区：
文献类型：
--
作者：
Matsumoto, Ayumi;Nagashima, Masako;Osaka, Hitoshi
简介：神经元蜡样脂肪沉积症（neuronalceroidlipoluscinoses，NCLs; CLN）是一种常染色体隐性遗传的神经退行性疾病，其特征是神经元和其他细胞内自发荧光脂肪沉积。症状包括视力障碍、运动能力下降和癫痫。致病基因为CLN 1、CLN 2、CLN 3、CLN 5、CLN 6、CLN 7、CLN 8、CLN 10、CLN 11、CLN 12、CLN 13和CLN 14。我们提出了第四例日本CLN 6突变。病例介绍：在3岁，我们的病人变得笨拙，容易摔倒。患者出现局灶性癫痫发作伴意识受损，开始接受卡马西平治疗。他表现出共济失调性行走和构音障碍，并伴有深层腱反射增加。发作间期脑电图显示左侧颞枕区慢波。脑磁共振成像显示小脑萎缩和脑室扩大。在光学相干断层扫描（OCT）中，视网膜的内层很厚，反射率很高。外显子组测序发现一个已知的纯合突变，C.794_976del，p.（Ser 265 del）在CLN 6中。讨论：全球共报告了130例CLN 6突变的NCL病例，其中只有4例来自日本，包括目前的患者。在6例病例中报告了265位丝氨酸的缺失。Ser 265位于易发生突变的短重复序列区域。使用腺相关病毒血清型9的基因治疗的临床试验已经开始用于NCL 6，使得早期诊断至关重要。OCT检查可能有助于诊断。(C)2019日本儿童神经病学学会。Elsevier B. V.出版，保留所有权利。
Introduction: Neuronal ceroid lipoluscinoses (NCLs; CLN) are mainly autosomal recessive neurodegenerative disorders characterized by the accumulation of autofluoreseent lipopigments in neuronal and other cells. Symptoms include visual disabilities, motor decline, and epilepsy. Causative genes arc CLN1, CLN2, CLN3, CLN5, CLN6, CLN7, CLN8, CLN10, CLN11, CLN12, CLN13, and CLN14. We present the fourth Japanese case with a CLN6 mutation.Case presentation: At 3 years of age, our patient became clumsy and fell down easily. He developed focal seizures with impaired consciousness and was started on carbamazepine. He showed ataxic walking and dysarthria with increased deep tendon reflexes. Interictal electroencephalogram revealed slow waves in the left temporal and occipital areas. Brain magnetic resonance imaging showed cerebellar atrophy and ventriculomegaly. In optical coherence tomography (OCT), the inner layer of the retina was thick and highly reflective. Exome sequencing revealed a known homozygous mutation, C.794_976del, p. (Ser265del) in CLN6.Discussion: A total of 130 cases of NCL with CLN6 mutations have been reported globally, of which only four were from Japan including the current patient. The deletion of serine at position 265 has been reported in six cases. Ser265 is located in a region of short repeated sequences that is susceptible to mutation. Clinical trials of gene therapy using adeno-associated virus serotype 9 have started for NCL6, making early diagnosis crucial. OCT examination might be helpful in achieving a diagnosis. (C) 2019 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.