Leber's hereditary optic neuropathy plus dystonia caused by the mitochondrial ND1 gene m.4160 T > C mutation

被引:6
作者
Ren, Hong [1 ,2 ]
Lin, Yan [1 ,2 ]
Li, Ying [3 ,4 ]
Zhang, Xiufang [1 ,2 ]
Wang, Wei [1 ,2 ]
Xu, Xuebi [5 ]
Ji, Kunqian [1 ,2 ]
Zhao, Yuying [1 ,2 ]
Yan, Chuanzhu [1 ,2 ,6 ,7 ]
机构
[1] Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Res Inst Neuromuscular & Neurodegenerat Dis, 107 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China
[2] Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Neurol, 107 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China
[3] Shandong Univ, Qilu Hosp, Dept Geriatr Med, Jinan 250012, Shandong, Peoples R China
[4] Shandong Univ, Qilu Hosp, Key Lab Cardiovasc Prote Shandong Prov, Jinan 250012, Shandong, Peoples R China
[5] Wenzhou Med Univ, Affiliated Hosp 1, Dept Neurol, Nanbaixiang St, Wenzhou 325000, Peoples R China
[6] Shandong Univ, Qilu Hosp Qingdao, Mitochondrial Med Lab, Qingdao 266035, Shandong, Peoples R China
[7] Shandong Univ, Brain Sci Res Inst, Jinan 250000, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
LHON; Dystonia; Mitochondrial DNA; ND1; gene; Mutation; Complex I; COMPLEX-I DEFICIENCY; CAUSATIVE MUTATION; MT-ND1; MTDNA; IDENTIFICATION; EXPRESSION; DISORDERS; MELAS;
D O I
10.1007/s10072-022-06165-x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background Leber's hereditary optic neuropathy (LHON) is a common mitochondrial disease. More than 30 variants in the mitochondrial DNA (mtDNA) have been previously described in LHON. However, the pathogenicity of some variants remains unclear. Herein, we report a 19-year-old boy presenting unique LHON plus dystonia syndrome with the rare m.4136A > G and m.4160 T > C variants and elucidate the molecular pathomechanisms of the m.4160 T > C mutation. Methods We performed clinical, molecular genetic analysis, and biochemical investigation in the patient's different tissues and cybrid cell lines. Results The optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) of the patient showed typical pathological changes-a significant decrease in the 17 thickness of the retinal nerve fiber layer (RNFL) and the ganglion cell complex (GCC). Brain magnetic resonance imaging (MRI) found noteworthy abnormal signals in the basal ganglia region. The genetic analysis revealed that the m.4160 T > C variant was heteroplasmic in the blood ( 80.2%), urine sediment (90.8%), and oral mucosal (81.7%) samples of the patient. In contrast, the m.4136A > G variant was homoplasmic in all available tissues. Biochemical and bioenergetic investigations showed decreased mitochondrial protein levels and mitochondrial respiration deficiency in cybrid cells harboring these variants. Conclusions This research provided more comprehensive data to help gain insight into the pathogenicity of the m.4160 T > C variant and broaden our view on the LHON plus phenotype.
引用
收藏
页码:5581 / 5592
页数:12
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