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A Homoplasmic MT‐TV Mutation Associated with Mitochondrial Inheritance of Hereditary Spastic Paraplegia
Movement Disorders ( IF 7.4 ) Pub Date : 2024-10-29 , DOI: 10.1002/mds.30048 Yan Shi, Junhao Xie, Junyi Jiang, Xinyu Yan, Xuejiao Chen, Shunyan Hong, Jiyuan Liu, Guorong Xu, Huizhen Su, Wanjin Chen, Ning Wang, Xiang Lin
Movement Disorders ( IF 7.4 ) Pub Date : 2024-10-29 , DOI: 10.1002/mds.30048 Yan Shi, Junhao Xie, Junyi Jiang, Xinyu Yan, Xuejiao Chen, Shunyan Hong, Jiyuan Liu, Guorong Xu, Huizhen Su, Wanjin Chen, Ning Wang, Xiang Lin
BackgroundHereditary spastic paraplegia (HSP) is characterized by progressive lower limb weakness and spasticity, with unknown genetic cause in many cases.ObjectivesTo identify novel genetic causes of HSP.MethodsPhenotypic characterization, genetic screening, transcriptome sequencing, and peroneal nerve biopsy were conducted in a Chinese HSP family.ResultsWe found a homoplasmic MT‐TV (mitochondrial tRNAVal ) mutation, m.1661A > G, present in all affected individuals across four generations of a family with complex HSP. Fourth‐generation affected individuals displayed earlier onset, likely due to presumptive anticipation, and greater symptom severity, potentially caused by decreased mitochondrial DNA (mtDNA) copy number. Upregulation of mitochondrial autophagy genes in these patients suggested that MT‐TV mutations could lead to reduced mtDNA copy number. Neural biopsies revealed ultrastructural abnormalities in myelin and mitochondria.ConclusionsThe rare MT‐TV m.1661A > G mutation is associated with HSP. Variations in mtDNA copy number may play a causal role in differences among clinical phenotypes. © 2024 International Parkinson and Movement Disorder Society.
更新日期：2024-10-29
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