Hori Ikumi, Ieda Daisuke, Ito Shogo, Ebe Seimi, Nakamura Yuji, Ohashi Kei, Aoyama Kohei, Hattori Ayako, Kokubo Minoru, Saitoh Shinji
Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Japan; Department of Pediatrics, Aichi Prefectural Welfare Federation of Agricultural Cooperatives Kainan Hospital, Japan.
Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Japan.
Brain Dev. 2021 Apr;43(4):590-595. doi: 10.1016/j.braindev.2020.12.008. Epub 2021 Jan 2.
Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is a non-catalytic component of the multi-tRNA synthetase complex that catalyzes the ligation of amino acids to their correct tRNAs. Bi-allelic truncating variants in the AIMP1 gene have been associated with hypomyelinating leukodystrophy-3 (HLD3; MIM 260600), which is characterized by hypomyelination, microcephaly, seizures and decreased life expectancy. Although peripheral nerve involvement has been assumed for HLD3, no compelling evidence is available to date.
The case was a first-born Filipino male. He showed profound developmental delay, failure to thrive, and spasticity in his limbs. At three months of age he developed refractory epilepsy. Serial magnetic resonance imaging (MRIs) showed profound myelination delay and progressive cerebral atrophy. He showed abnormal nerve conduction studies. Genetic testing revealed a homozygous pathogenic variant in the AIMP1 gene (NM_004757.3: c.115C > T: p.Gln39*). The parents were heterozygous for the same variant.
Here, we report a patient with a homozygous nonsense AIMP1 variant showing peripheral neuropathy as well as HLD3. Our case suggests that AIMP1 plays a pivotal role in the peripheral nerve as well as the central nervous system.
氨酰 - tRNA合成酶相互作用多功能蛋白1（AIMP1）是多tRNA合成酶复合物的非催化成分，该复合物催化氨基酸与正确的tRNA连接。AIMP1基因的双等位基因截短变异与低髓鞘性脑白质营养不良3型（HLD3；MIM 260600）相关，其特征为髓鞘形成减少、小头畸形、癫痫发作和预期寿命缩短。尽管HLD3被认为会累及周围神经，但迄今为止尚无确凿证据。
该病例为一名菲律宾裔头胎男性。他表现出严重的发育迟缓、生长发育不良和肢体痉挛。三个月大时出现难治性癫痫。系列磁共振成像（MRI）显示严重的髓鞘形成延迟和进行性脑萎缩。他的神经传导研究结果异常。基因检测发现AIMP1基因（NM_004757.3：c.115C>T：p.Gln39*）存在纯合致病性变异。父母为该变异的杂合子。
在此，我们报告一名患有纯合无义AIMP1变异的患者，其表现出周围神经病变以及HLD3。我们的病例表明AIMP1在周围神经以及中枢神经系统中起关键作用。
