PDF(Pubmed)
Abstract：
BACKGROUND: NARS2 as a member of aminoacyl-tRNA synthetases was necessary to covalently join a specific tRNA to its cognate amino acid. Biallelic variants in NARS2 were reported with disorders such as Leigh syndrome, deafness, epilepsy, and severe myopathy.
METHODS: Detailed clinical phenotypes were collected and the NARS2 variants were discovered by whole exome sequencing and verified by Sanger sequencing. Additionally, 3D protein structure visualization was performed by UCSF Chimera. The proband in our study had early-onset status epilepticus with abnormal EEG and MRI results. She also performed global developmental delay (GDD) and myocardial dysfunction. Next-generation sequencing (NGS) and Sanger sequencing revealed compound heterozygous missense variants [NM_024678.6:exon14: c.1352G > A(p.Arg451His); c.707T > C(p.Phe236Ser)] of the NARS2 gene. The proband develops refractory epilepsy with GDD and hyperlactatemia. Unfortunately, she finally died for status seizures two months later.
CONCLUSIONS: We discovered two novel missense variants of NARS2 in a patient with early-onset status epilepticus and myocardial dysfunction. The NGS enables the patient to be clearly diagnosed as combined oxidative phosphorylation deficiency 24 (COXPD24, OMIM:616,239), and our findings expands the spectrum of gene variants in COXPD24.
METHODS: Detailed clinical phenotypes were collected and the NARS2 variants were discovered by whole exome sequencing and verified by Sanger sequencing. Additionally, 3D protein structure visualization was performed by UCSF Chimera. The proband in our study had early-onset status epilepticus with abnormal EEG and MRI results. She also performed global developmental delay (GDD) and myocardial dysfunction. Next-generation sequencing (NGS) and Sanger sequencing revealed compound heterozygous missense variants [NM_024678.6:exon14: c.1352G > A(p.Arg451His); c.707T > C(p.Phe236Ser)] of the NARS2 gene. The proband develops refractory epilepsy with GDD and hyperlactatemia. Unfortunately, she finally died for status seizures two months later.
CONCLUSIONS: We discovered two novel missense variants of NARS2 in a patient with early-onset status epilepticus and myocardial dysfunction. The NGS enables the patient to be clearly diagnosed as combined oxidative phosphorylation deficiency 24 (COXPD24, OMIM:616,239), and our findings expands the spectrum of gene variants in COXPD24.
摘要：
背景：NARS2作为氨酰基-tRNA合成酶的成员对于将特定的tRNA共价连接到其同源氨基酸是必需的。据报道，NARS2中的双等位基因变体患有Leigh综合征等疾病，耳聋,癫痫,和严重的肌病.
方法：收集详细的临床表型，通过全外显子组测序发现NARS2变异，并通过Sanger测序进行验证。此外,通过UCSF嵌合体进行3D蛋白质结构可视化。我们研究中的先证者患有早发性癫痫持续状态，脑电图和MRI结果异常。她还进行了整体发育迟缓（GDD）和心肌功能障碍。下一代测序（NGS）和Sanger测序揭示了复合杂合错义变体[NM_024678.6：exon14：c.1352G>A（p。Arg451His）；c.707T>C（p。Phe236Ser)]的NARS2基因。先证者发展为GDD和高乳酸血症的难治性癫痫。不幸的是,两个月后，她终于因癫痫发作而死亡。
结论：我们在一名早发性癫痫持续状态和心肌功能障碍患者中发现了两种新的NARS2错义变异。NGS可以明确诊断为合并氧化磷酸化缺陷24（COXPD24，OMIM：616,239），我们的发现扩大了COXPD24基因变异的范围。
方法：收集详细的临床表型，通过全外显子组测序发现NARS2变异，并通过Sanger测序进行验证。此外,通过UCSF嵌合体进行3D蛋白质结构可视化。我们研究中的先证者患有早发性癫痫持续状态，脑电图和MRI结果异常。她还进行了整体发育迟缓（GDD）和心肌功能障碍。下一代测序（NGS）和Sanger测序揭示了复合杂合错义变体[NM_024678.6：exon14：c.1352G>A（p。Arg451His）；c.707T>C（p。Phe236Ser)]的NARS2基因。先证者发展为GDD和高乳酸血症的难治性癫痫。不幸的是,两个月后，她终于因癫痫发作而死亡。
结论：我们在一名早发性癫痫持续状态和心肌功能障碍患者中发现了两种新的NARS2错义变异。NGS可以明确诊断为合并氧化磷酸化缺陷24（COXPD24，OMIM：616,239），我们的发现扩大了COXPD24基因变异的范围。
