RARS2 mutations in a sibship with infantile spasms.
RARS2 mutations in a sibship with infantile spasms.
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DOI：
10.1111/epi.13358
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发表时间：
2016-05
期刊：
影响因子：
5.6
通讯作者：
Kurian MA
中科院分区：
文献类型：
--
作者：
Ngoh A;Bras J;Guerreiro R;Meyer E;McTague A;Dawson E;Mankad K;Gunny R;Clayton P;Mills PB;Thornton R;Lai M;Forsyth R;Kurian MA
桥小脑发育不全是一组异质性神经发育障碍，其特征是脑干和小脑体积减小。我们报告了两名男性兄弟姐妹，他们出现早期婴儿阵挛性癫痫发作，然后出现婴儿痉挛症，并在磁共振成像（MRI）上发现明显的孤立性小脑发育不全/萎缩。使用全外显子组测序技术，发现两者都是先前报道的一种复合杂合子，以及编码线粒体精氨酰-tRNA 合成酶 2 (RARS2) 的基因中的一种新突变。该基因的突变在六型脑桥小脑发育不全（PCH6）中被典型地描述，这种表型的特征是早期（通常是顽固性）癫痫发作、严重发育迟缓和进行性脑桥小脑萎缩。 PCH6 的电临床谱很广泛，包括多种癫痫发作类型：肌阵挛性癫痫发作、全身强直阵挛性癫痫发作和局灶性阵挛性癫痫发作。我们的报告扩展了 PCH6 疾病谱的特征，并将婴儿痉挛症作为相关的电临床表型。
Pontocerebellar hypoplasia is a group of heterogeneous neurodevelopmental disorders characterized by reduced volume of the brainstem and cerebellum. We report two male siblings who presented with early infantile clonic seizures, and then developed infantile spasms associated with prominent isolated cerebellar hypoplasia/atrophy on magnetic resonance imaging (MRI). Using whole exome sequencing techniques, both were found to be compound heterozygotes for one previously reported and one novel mutation in the gene encoding mitochondrial arginyl‐tRNA synthetase 2 (RARS2). Mutations in this gene have been classically described in pontocerebellar hypoplasia type six (PCH6), a phenotype characterized by early (often intractable) seizures, profound developmental delay, and progressive pontocerebellar atrophy. The electroclinical spectrum of PCH6 is broad and includes a number of seizure types: myoclonic, generalized tonic–clonic, and focal clonic seizures. Our report expands the characterization of the PCH6 disease spectrum and presents infantile spasms as an associated electroclinical phenotype.