Leber's Hereditary Optic Neuropathy–Specific Heteroplasmic Mutation m.14495A>G Found in a Chinese Family
| Autor: | Shan Duan, Kaifeng Zheng, Xueying Gu, Lin Sheng, Yueyuan Qin, Xi Li, Keqin Yao, Baojiang Wang, Linghua Zhang, Shouqing Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Mitochondrial DNA congenital hereditary and neonatal diseases and abnormalities Lineage (genetic) genetic structures mtDNA copy number Biomedical Engineering Biology Haplogroup 03 medical and health sciences symbols.namesake LHON 0302 clinical medicine medicine Digital polymerase chain reaction heteroplasmy Sanger sequencing Genetics dPCR m.14495A>G Leber's hereditary optic neuropathy Articles medicine.disease Heteroplasmy eye diseases Ophthalmology 030104 developmental biology Mutation (genetic algorithm) 030221 ophthalmology & optometry symbols |
| Zdroj: | Translational Vision Science & Technology |
| ISSN: | 2164-2591 |
| Popis: | Purpose Leber's hereditary optic neuropathy (LHON) is a mitochondrial DNA (mtDNA)-associated, maternally inherited eye disease. Mutation heteroplasmy level is one of the leading causes to trigger LHON manifestation. In this study, we aimed to identify the causative mutation in a large Han Chinese family with LHON and explore the underlying pathogenic mechanism in this LHON family. Methods The whole-mtDNA sequence was amplified by long-range PCR. Mutations were subsequently identified by next-generation sequencing (NGS) and validated by Sanger sequencing. The heteroplasmy rates of those family members were determined by digital PCR (dPCR). Mitochondrial haplogroups were assigned based on mtDNA tree build 17. Results The m.14495A>G mutation was identified as causative due to its higher heteroplasmy level (>50%) in patients than in their unaffected relatives. All mutation carriers belong to M7b1a1 and are assigned to Asian mtDNA lineage. Interestingly, our result revealed that high mtDNA copy number in carrier might prevent LHON manifestation. Conclusions This is the first report of m.14495A>G mutation in Asian individuals with LHON. Our study shows that dPCR technology can provide more reliable results in mutation heteroplasmy assay and determination of the cellular mtDNA content, making it a potentially promising tool for clinical precise diagnosis of LHON. Furthermore, our results also add evidence to the opinion that higher mtDNA content may protect mutation carriers from LHON. Translational relevance dPCR can be used for the assessment of LHON disease, and a new genetic-based diagnostic strategy has been proposed for LHON patients with the m.14495A>G mutation. |
| Databáze: | OpenAIRE |
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