丙氨酰-tRNA 合成酶 2（AARS2）相关性小脑共济失调而无脑白质病。
Alanyl-tRNA Synthetase 2 (AARS2)-Related Ataxia Without Leukoencephalopathy.
机构信息
Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI, USA.
Medical Scientist Training Program, University of Michigan, Ann Arbor, MI, USA.
出版信息
Cerebellum. 2020 Feb;19(1):154-160. doi: 10.1007/s12311-019-01080-y.
Abstract
Mutations in the mitochondrial alanyl-tRNA synthetase gene, AARS2, have been reported to cause leukoencephalopathy associated with early ovarian failure, a clinical presentation described as "ovarioleukodystrophy." We present a sibling pair: one with cerebellar ataxia and one with vision loss and cognitive impairment in addition to ataxia. Neither shows evidence of leukoencephalopathy on MRI imaging. Exome sequencing revealed that both siblings are compound heterozygous for AARS2 variants (p.Phe131del and p.Ile328Met). Yeast complementation assays indicate that p.Phe131del AARS2 dramatically impairs gene function and that p.Ile328Met AARS2 is a hypomorphic allele. This work expands the phenotypic spectrum of AARS2-associated disease to include ataxia without leukoencephalopathy.
摘要
线粒体丙氨酰-tRNA 合成酶基因（AARS2）的突变已被报道可导致与卵巢早衰相关的脑白质病，这种临床表现被描述为“卵巢脑白质营养不良症”。我们介绍了一对同胞兄妹：一位表现为小脑共济失调，另一位除了共济失调外还有视力丧失和认知障碍。磁共振成像（MRI）检查均未显示脑白质病的证据。外显子组测序显示，这对兄妹均为 AARS2 变异（p.Phe131del 和 p.Ile328Met）的复合杂合子。酵母互补实验表明，p.Phe131del AARS2 严重损害了基因功能，而 p.Ile328Met AARS2 是一个功能降低的等位基因。这项工作扩展了 AARS2 相关疾病的表型谱，包括不伴有脑白质病的共济失调。
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