AIMP1 Mutation Long-Term Follow-Up, With Decreased Brain N-Acetylaspartic Acid and Secondary Mitochondrial Abnormalities
AIMP1 Mutation Long-Term Follow-Up, With Decreased Brain N-Acetylaspartic Acid and Secondary Mitochondrial Abnormalities
复制标题
AIMP1突变长期随访，脑N-乙酰天冬氨酸减少和继发性线粒体异常
作者：
Aneal Khan;Jennifer Bennett;Morris H. Scantlebury;X. Wei;M. Kerr
氨酰转移 RNA (tRNA) 合成酶复合物相互作用多功能蛋白 I 是 tRNA 多合成酶复合物的非催化成分。尽管 AIMP1 在连接 tRNA 与其同源氨基酸方面很重要，但它还具有多种其他功能，包括轴突生长、细胞因子活性以及与核糖体 tRNA 合成酶复合物中 N-乙酰天冬氨酸的相互作用。此外，N-乙酰天冬氨酸在髓鞘形成过程中提供天冬氨酸，因此对轴突完整性很重要。 AIMP1 突变会破坏这些功能，正如对 2 个同卵双胞胎的临床案例研究所证明的那样，这对双胞胎表现出先天性角弓反张、小头畸形、严重发育迟缓和癫痫发作。全外显子组测序用于识别 AIMP1 基因中的过早终止密码子 (g. 107248613_c.115C>T; p.(Gln39)。在缺乏全外显子组测序的情况下，我们提出磁共振波谱上减少的 N-乙酰天冬氨酸峰可以作为 AIMP1 突变的生物标志物。
Aminoacyl transfer RNA (tRNA) synthetase complex-interacting multifunctional protein I is a noncatalytic component of tRNA multi-synthetase complexes. Although important in joining tRNAs to their cognate amino acids, AIMP1 has several other functions including axonal growth, cytokine activity, and interactions with N-acetylaspartic acid in ribosomal tRNA synthetase complexes. Further, N-acetylaspartic acid donates an aspartate during myelination and is therefore important to axonal integrity. Mutations in AIMP1 can disrupt these functions, as demonstrated in this clinical case study of 2 monozygotic twins, who display congenital opisthotonus, microcephaly, severe developmental delay, and seizures. Whole exome sequencing was used to identify a premature stop codon in the AIMP1 gene (g. 107248613_c.115C>T; p.(Gln39). In the absence of whole exome sequencing, we propose that decreased N-acetylaspartic acid peaks on magnetic resonance spectroscopy could act as a biomarker for AIMP1 mutations.
影响因子：
7
作者：
Giardine, B;Riemer, C;Nekrutenko, A
通讯作者：
Nekrutenko, A
影响因子：
8.8
作者：
Gonzaga-Jauregui C;Harel T;Gambin T;Kousi M;Griffin LB;Francescatto L;Ozes B;Karaca E;Jhangiani SN;Bainbridge MN;Lawson KS;Pehlivan D;Okamoto Y;Withers M;Mancias P;Slavotinek A;Reitnauer PJ;Goksungur MT;Shy M;Crawford TO;Koenig M;Willer J;Flores BN;Pediaditrakis I;Us O;Wiszniewski W;Parman Y;Antonellis A;Muzny DM;Baylor-Hopkins Center for Mendelian Genomics;Katsanis N;Battaloglu E;Boerwinkle E;Gibbs RA;Lupski JR
通讯作者：
Lupski JR