The genotypic and phenotypic spectrum of PARS2-related infantile-onset encephalopathy
The genotypic and phenotypic spectrum of PARS2-related infantile-onset encephalopathy
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PARS2相关婴儿发病脑病的基因型和表型谱
DOI：
10.1038/s10038-018-0478-z
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发表时间：
2018-09-01
影响因子：
3.5
通讯作者：
Li, Nan
中科院分区：
文献类型：
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作者：
Yin, Xiaomeng;Tang, Beisha;Li, Nan
线粒体氨基酰-tRNA合成酶(mt-AARs)是一类在蛋白质生物合成中起关键作用的酶家族。Mt-AARs的突变与多种疾病有关。作为mt-Aars家族的一员，编码Prolyl-tRNA合成酶2的PARS2基因最近被证明与Alpers综合征和某些婴儿起病的神经退行性疾病有关。在此，我们报告了两例早期发育迟缓、癫痫痉挛、髓鞘形成延迟并伴有小脑白质异常、进行性皮质萎缩的患者。全外显子测序发现PARS2中存在致病化合物杂合变异[c.283G>；A(p.95V>；I)]和[c.604G>；C(p.202R>；G)]。几乎所有患者都有癫痫痉挛，对治疗有早期反应，早期发育延迟和/或退化，随后出现全身低眼压、出生后小头畸形、乳酸水平升高和进行性脑萎缩。我们的研究为验证PARS2在相关婴儿脑病的病理中的作用提供了进一步的证据，有助于该疾病的表型特征，并为该疾病的诊断提供了临床和分子方面的见解。
Mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) are a family of enzymes that play critical roles in protein biosynthesis. Mutations in mt-aaRSs are associated with various diseases. As a member of the mt-aaRS family, PARS2 encoding prolyl-tRNA synthetase 2 was recently shown to be associated with Alpers syndrome and certain infantile-onset neurodegenerative disorders in four patients. Here, we present two patients in a pedigree with early developmental delay, epileptic spasms, delayed myelination combined with cerebellar white matter abnormalities, and progressive cortical atrophy. Whole-exome sequencing revealed pathogenic compound heterozygous variants [c.283 G > A (p.95 V > I)] and [c.604 G > C (p.202 R > G)] in PARS2. Nearly all patients had epileptic spasms with early response to treatment, early developmental delay and/or regression followed by generalized hypotonia, postnatal microcephaly, elevated lactate levels, and progressive cerebral atrophy. Our study provides further evidence for validating the role of PARS2 in the pathology of related infantile-onset encephalopathy, contributing to the phenotypic features of this condition, and providing clinical and molecular insight for the diagnosis of this disease entity.