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Neurological Sciences

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14.06.2022 | Original Article

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

verfasst von: Hong Ren, Yan Lin, Ying Li, Xiufang Zhang, Wei Wang, Xuebi Xu, Kunqian Ji, Yuying Zhao, Chuanzhu Yan

Erschienen in: Neurological Sciences | Ausgabe 9/2022

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Abstract

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.

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Titel: Leber’s hereditary optic neuropathy plus dystonia caused by the mitochondrial ND1 gene m.4160 T > C mutation
verfasst von: Hong Ren
Yan Lin
Ying Li
Xiufang Zhang
Wei Wang
Xuebi Xu
Kunqian Ji
Yuying Zhao
Chuanzhu Yan
Publikationsdatum: 14.06.2022
Verlag: Springer International Publishing
Erschienen in: Neurological Sciences / Ausgabe 9/2022
Print ISSN: 1590-1874
Elektronische ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-022-06165-x

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