Division of Pediatric Neurology, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
Division of Neuroradiology, Department of Radiology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
Pediatr Neurol. 2019 Feb;91:57-61. doi: 10.1016/j.pediatrneurol.2018.09.010. Epub 2018 Sep 25.
Mutations in AIMP1, which plays an important role in the development and maintenance of axon-cytoskeleton integrity and regulating neurofilaments, cause neurodegeneration of variable severity and white matter abnormalities.
From the patient records we analyzed the clinical evaluation, molecular genetics, neurodiagnostic, and neuroradiological investigations.
We describe six members of a large consanguineous family with a phenotype of severe neurodegeneration in the form of developmental delays, progressive microcephaly, epilepsy, and failure to thrive. MRI showed callosal atrophy and T2 hyperintensity in the superficial white matter. The periventricular and deep white matter structures were, however, preserved. MR spectroscopy demonstrated N-acetylaspartate preservation without evidence of neuroinflammation. Exome sequencing showed a novel homozygous mutation of the AIMP1 gene in all individuals: c.917A>G (p.(Asp306Gly)).
This novel homozygous mutation of the AIMP1 gene is characterized by preserved development of the periventricular and deep white matter structures as demonstrated by MRI and MR spectroscopy correlation.
AIMP1 突变会导致轴突细胞骨架完整性的发育和维持以及神经丝的调节发生神经退行性变，其导致的神经退行性变的严重程度和白质异常具有可变性。
我们从患者的病历中分析了临床评估、分子遗传学、神经诊断和神经影像学研究。
我们描述了一个大型近亲家族的六名成员，他们的表型为严重的神经退行性变，表现为发育迟缓、进行性小头畸形、癫痫发作和生长不良。MRI 显示胼胝体萎缩和浅白质 T2 高信号。然而，脑室周围和深部白质结构得以保留。磁共振波谱分析显示 N-乙酰天门冬氨酸保留，没有神经炎症的证据。外显子组测序显示所有个体中 AIMP1 基因的新型纯合突变：c.917A>G(p.(Asp306Gly))。
这种新型的 AIMP1 基因突变的特征是通过 MRI 和磁共振波谱相关性显示脑室周围和深部白质结构的发育得以保留。
