Novel m.3764C>G variant in MT-ND1 linked to severe MELAS syndrome: A case report

Teona Shatirishvili , Zura Katsitadze , Yi Shiau Ng , Ashwin Achuthaprasad , Charlotte L. Alston , Emma L. Blakey , Douglass M. Turnbull , Kakha Bregvadze , Tinatin Tkemaladze , Nana Nino Tatishvili
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Abstract

Background

MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a multisystem disorder with diverse clinical presentations. Approximately 80 % of MELAS cases are linked to the m.3243A>G pathogenic variant in the MT-TL1. Pathogenic variants in other mtDNA genes, including MT-ND1, can also cause MELAS. We report a case of MELAS in a 16-year-old boy with a novel m.3764C>G variant in the MT-ND1.

Case presentation

A 9 years old male patient developed bilateral sensorineural hearing loss followed by a generalized tonic-clonic seizure. At 15, he exhibited progressive fatigue, muscle weakness, and stroke-like episodes. MRI revealed stroke-like lesions in the brain. Over two years, he experienced multiple hospital admissions for severe symptoms including right-sided hemiparesis, hemianopia, seizures, and encephalopathy. Despite treatment, his condition deteriorated, leading to multi-organ failure and death at 16. Molecular genetic analysis identified a heteroplasmic m.3764C>G variant in MT-ND1.

Discussion/Conclusion

Presented case highlights the novel m.3764C>G variant in MT-ND1 associated with MELAS, emphasizing the variant's pathogenicity based on its absence in human mitochondrial databases, de novo occurrence, and predicted severe impact on ND1 protein function. The patient's rapidly progressive disease course contrasts with typical MELAS trajectories, underscoring the variant's severity. This report expands the clinical and mutational spectrum of MELAS and underscores the need for further research into MT-ND1 related MELAS.
MT-ND1中与严重MELAS综合征相关的新型m.3764C >g变异:一例报告
melas(线粒体脑肌病、乳酸性酸中毒和卒中样发作)是一种多系统疾病,具有多种临床表现。大约80%的MELAS病例与MT-TL1中的m.3243A>;G致病性变体有关。其他mtDNA基因的致病变异,包括MT-ND1,也可引起MELAS。我们报告一例MELAS在一个16岁的男孩与一个新的m.3764C>;G变异MT-ND1。病例表现:一名9岁男性患者出现双侧感音神经性听力丧失,随后出现全身性强直-阵挛性癫痫发作。15岁时,他表现出进行性疲劳、肌肉无力和中风样发作。核磁共振成像显示脑部有类似中风的病变。两年多来,他多次因严重症状入院,包括右侧偏瘫、偏视、癫痫发作和脑病。尽管接受了治疗,但他的病情恶化,导致多器官衰竭,16岁时死亡。分子遗传分析在MT-ND1中鉴定出m.3764C>;G异质变异。讨论/结论本病例强调了与MELAS相关的MT-ND1中新的m.3764C>;G变异,强调了该变异基于其在人类线粒体数据库中缺失,从头发生,并预测对ND1蛋白功能的严重影响的致病性。患者快速进展的病程与典型的MELAS轨迹形成对比,强调了该变体的严重程度。本报告扩展了MELAS的临床和突变谱,并强调了进一步研究MT-ND1相关MELAS的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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