PARS2 and NARS2 mutations in infantile-onset neurodegenerative disorder
PARS2 and NARS2 mutations in infantile-onset neurodegenerative disorder
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DOI：
10.1038/jhg.2016.163
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发表时间：
2017-05-01
影响因子：
3.5
通讯作者：
Matsumoto, Naomichi
中科院分区：
文献类型：
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作者：
Mizuguchi, Takeshi;Nakashima, Mitsuko;Matsumoto, Naomichi
在这里，我们提出了四个不相关的家庭与六个人有癫痫发作的发育迟缓/退化和癫痫。全外显子组测序显示复合杂合突变，c. [283G>A];[607 G>A]在一个家族中编码脯氨酰-tRNA合成酶（PARS 2）的基因中。两对复合杂合突变，c。[151C>T];[1184T>G]和c. [707T>G];[594+1G>A]，和纯合突变，c. [500A>G];[500 A>G]，在编码天冬酰胺酰-tRNA合成酶（NARS 2）的基因中也鉴定出。编码氨酰-tRNA合成酶的基因突变导致基因特异性线粒体疾病。据报道，双等位基因PARS 2或NARS 2突变可引起阿尔珀斯综合征，这是一种常染色体隐性遗传神经退行性疾病，其特征为精神退行性疾病和癫痫，伴有不同程度的肝脏受累。此外，已知NARS 2突变引起各种临床表型，包括非综合征性听力损失、Leigh综合征、癫痫智力残疾和严重肌病。我们在这里报告的具有PARS 2和NARS 2突变的个体表现出与之前报告的相似的神经系统特征，但临床表现多样性，例如听力损失和癫痫发作类型。我们的数据拓宽了PARS 2和NARS 2相关疾病的临床和突变谱。
Here we present four unrelated families with six individuals that have infantile-onset developmental delay/regression and epilepsy. Whole-exome sequencing revealed compound heterozygous mutations, c.[283G>A];[607G>A] in a gene encoding prolyl-tRNA synthetase (PARS2) in one family. Two pairs of compound heterozygous mutations, c.[151C>T];[1184T>G] and c. [707T>G];[594+1G>A], and a homozygous mutation, c.[500A>G];[500A>G], in a gene encoding asparaginyl-tRNA synthetase (NARS2) were also identified in the other three families. Mutations in genes encoding aminoacyl-tRNA synthetases cause gene-specific mitochondrial disorders. Biallelic PARS2 or NARS2 mutations are reported to cause Alpers' syndrome, which is an autosomal recessive neurodegenerative disorder characterized by psychomotor regression and epilepsy with variable degree of liver involvement. Moreover, it is known that NARS2 mutations cause various clinical phenotypes, including non-syndromic hearing loss, Leigh syndrome, intellectual disability with epilepsy and severe myopathy. The individuals with PARS2 and NARS2 mutations, we have reported here demonstrate similar neurological features as those previously reported, with diversity in clinical presentation such as hearing loss and seizure type. Our data broaden the clinical and mutational spectrum of PARS2-and NARS2-related disorders.