Department of Neurology, Qilu hospital of Shandong University, Jinan, China.
J Hum Genet. 2019 Oct;64(10):979-983. doi: 10.1038/s10038-019-0648-7. Epub 2019 Aug 6.
Leukodystrophies are genetic disorders leading to progressive white matter degeneration in the central nervous system. Mitochondrial aminoacyl tRNA synthase protein is encoded by the nuclear gene AARS2. An autosomal recessive mutation in this gene has been linked to AARS2 mutation-related adult-onset leukodystrophy (AARS2-L) or infantile mitochondrial cardiomyopathy. To date, only 16 AARS2-L cases have been reported in English literature. Thus, the clinical and genetic characteristics of this disease remain to be defined. Through whole-exome sequencing, we identified a Chinese patient with leukodystrophy related to two novel compounds heterozygous mutation in AARS2 (c.965 G > A, p.R322H; c.334 G > C, p.G112R). These two compounds heterozygous variants in AARS2 gene co-segregated with disease in his family. And pyramidal tracts in the spinal cord were involved. Our findings have important implications on genetic counseling for any case with leukodystrophy and extend the mutational spectrum in AARS2 gene.
脑白质营养不良是一种导致中枢神经系统进行性白质变性的遗传疾病。线粒体氨酰-tRNA 合成酶蛋白由核基因 AARS2 编码。该基因的常染色体隐性突变与 AARS2 突变相关的成人发病脑白质营养不良 (AARS2-L) 或婴儿期线粒体心肌病有关。迄今为止，仅在英文文献中报道了 16 例 AARS2-L 病例。因此，该疾病的临床和遗传特征仍有待确定。通过全外显子组测序，我们在一位脑白质营养不良患者中发现了两个与 AARS2 相关的新的复合杂合突变（c.965G>A，p.R322H；c.334G>C，p.G112R）。AARS2 基因中的这两个复合杂合变异与他的家族疾病共分离。并且脊髓中的锥体束也受到了影响。我们的发现对任何脑白质营养不良患者的遗传咨询都具有重要意义，并扩展了 AARS2 基因的突变谱。
