Identification of two novel null variants in CLN8 by targeted next-generation sequencing: first report of a Chinese patient with neuronal ceroid lipofuscinosis due to CLN8 variants.
Identification of two novel null variants in CLN8 by targeted next-generation sequencing: first report of a Chinese patient with neuronal ceroid lipofuscinosis due to CLN8 variants.
复制标题
通过靶向下一代测序鉴定 CLN8 中两个新的无效变异：首例中国患者因 CLN8 变异导致神经元蜡样质脂褐质沉着症的报告
DOI：
10.1186/s12881-018-0535-7
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发表时间：
2018-02-08
影响因子：
--
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Gao Z;Xie H;Jiang Q;Wu N;Chen X;Chen Q
神经元蜡样质脂褐质沉积症（Neuronalceroidlipofuscinoses，NCL）是儿童期最常见的神经退行性疾病之一，以癫痫发作、进行性认知功能下降、运动障碍和视力丧失为特征。在过去的二十年里，在受影响的患者中已经确定了13个候选基因中的430多个变异。大多数的变异几乎完全在西方患者的报告，和很少的临床和遗传信息可用于中国patients.Case presentationWe报告一个中国男孩的临床表型被怀疑是NCL，包括顽固性癫痫，认知和运动能力下降和进行性视力下降。使用靶向的下一代测序，在该患者的transmodel中检测到CLN 8中的两个新的无效变体（c.298C > T，p.Gln100Ter; c.551G > A，p.Trp184Ter）。根据美国医学遗传学和基因组学学会的变异指南，这两种变异被解释为致病性。我们的发现扩大了CLN 8的变异多样性，并证明了下一代靶向测序对儿科NCL的巨大诊断价值。
BackgroundNeuronal ceroid lipofuscinoses (NCLs) are one of the most frequent childhood-onset neurodegenerative pathologies characterized by seizures, progressive cognitive decline, motor impairment and loss of vision. For the past two decades, more than 430 variants in 13 candidate genes have been identified in the affected patients. Most of the variants were almost exclusively reported in Western patients, and very little clinical and genetic information was available for Chinese patients.Case presentationWe report a Chinese boy whose clinical phenotypes were suspected to be NCL, including intractable epilepsy, cognitive and motor decline and progressive vision loss. Using targeted next-generation sequencing, two novel null variants inCLN8(c.298C > T, p.Gln100Ter; c.551G > A, p.Trp184Ter) were detected in this patient intransmodel. These two variants were interpreted as pathogenic according to the variant guidelines of the American College of Medical Genetics and Genomics.ConclusionsThis is the first case report of NCL due toCLN8variants in China. Our findings expand the variant diversity ofCLN8and demonstrate the tremendous diagnosis value of targeted next-generation sequencing for pediatric NCLs.
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DOI：
10.1016/j.bbadis.2015.05.011
发表时间：
2015-10
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
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通讯作者：
Cotman SL
影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
9.8
作者：
Gao, HL;Boustany, RMN;MacDonald, ME
通讯作者：
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影响因子：
6.4
作者：
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通讯作者：
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