Clinical spectrum, treatment and outcomes of the m.10197G>A mutation in MT-ND3: a case report, systematic review and meta-analysis
Abstract Background A correlation between various sites or types of mutations in mitochondrial DNA ND3 and the development of a specific mitochondrial disease or phenotype has yet to be fully established. Methods This study reports a rare case of adult-onset Leigh syndrome (LS) and Leber hereditary...
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2025-02-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03588-5 |
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| author | YuZhi Shi Bin Chen SongTao Niu XinGao Wang ZaiQiang Zhang |
| author_facet | YuZhi Shi Bin Chen SongTao Niu XinGao Wang ZaiQiang Zhang |
| author_sort | YuZhi Shi |
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| description | Abstract Background A correlation between various sites or types of mutations in mitochondrial DNA ND3 and the development of a specific mitochondrial disease or phenotype has yet to be fully established. Methods This study reports a rare case of adult-onset Leigh syndrome (LS) and Leber hereditary optic neuropathy and dystonia (LDYT) overlap syndrome caused by the m.10197G>A mutation in ND3. A review of the literature was conducted to investigate the clinical spectrum, treatment and outcome resulting from the m.10197G>A mutation. Phenotypes associated with the m.10197G>A mutation were classified into three categories: LS/LS+ (LS-involved overlap syndrome), Leber hereditary optic neuropathy (LHON)/LHON+ (LHON-involved overlap syndrome) and other mitochondrial encephalopathies or presentations. Results A total of 84 participants (78 patients and 6 asymptomatic carriers) with the m.10197G>A mutation retrieved from 33 articles and the patient whose case we reported were included in the review and meta-analysis. Among all the participants, 55.3% (47/85) and 28.2% (24/85) presented with LS/LS+ and LHON/LHON+, respectively. The median age at onset for LS/LS+ was significantly younger than that for LHON/LHON+ [median, (Q1–Q3), 3.0 (0.58–9.5) vs. 13.5 (5.75–41.75), P = 0.001]. A negative linear correlation was observed between mutation load and age of onset in patients who presented with LS/LS+ (R2 = 0.592, P < 0.001), with the age of onset ranging from infancy to adulthood. Patients with an older age at onset [OR (95% CI), 1.46 (1.12–1.91), P = 0.005] or higher mutation loads [OR (95% CI), 1.14 (1.03–1.26), P = 0.011] were more likely to present with LHON/LHON+ than with LS/LS+. A total of 17 patients were documented as having received a combination of mitochondrial cofactor treatments. Compared with patients with LHON/LHON+, patients with LS/LS+ exhibited an exceedingly high probability of a stable or worsen outcome (93.8% vs. 33.3%, P = 0.006). Conclusions LS/LS+ and LHON/LHON+ are the predominant presentations of the m.10197G>A mutation. An older age at onset and greater mutation load increases the probability of an LHON/LHON+ presentation. Patients presenting with LS/LS+ have an exceedingly high possibility of an unfavorable outcome. The identification of factors and outcomes associated with phenotypes in patients with the m.10197G>A mutation facilitates the provision of improved prognostic counseling for patients and their family members who are carriers of this mutation. |
| format | Article |
| id | doaj-art-458e952f2b894b9eb9f643e8ca5ea0b7 |
| institution | Kabale University |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-458e952f2b894b9eb9f643e8ca5ea0b72025-02-09T12:54:03ZengBMCOrphanet Journal of Rare Diseases1750-11722025-02-0120111110.1186/s13023-025-03588-5Clinical spectrum, treatment and outcomes of the m.10197G>A mutation in MT-ND3: a case report, systematic review and meta-analysisYuZhi Shi0Bin Chen1SongTao Niu2XinGao Wang3ZaiQiang Zhang4Department of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityAbstract Background A correlation between various sites or types of mutations in mitochondrial DNA ND3 and the development of a specific mitochondrial disease or phenotype has yet to be fully established. Methods This study reports a rare case of adult-onset Leigh syndrome (LS) and Leber hereditary optic neuropathy and dystonia (LDYT) overlap syndrome caused by the m.10197G>A mutation in ND3. A review of the literature was conducted to investigate the clinical spectrum, treatment and outcome resulting from the m.10197G>A mutation. Phenotypes associated with the m.10197G>A mutation were classified into three categories: LS/LS+ (LS-involved overlap syndrome), Leber hereditary optic neuropathy (LHON)/LHON+ (LHON-involved overlap syndrome) and other mitochondrial encephalopathies or presentations. Results A total of 84 participants (78 patients and 6 asymptomatic carriers) with the m.10197G>A mutation retrieved from 33 articles and the patient whose case we reported were included in the review and meta-analysis. Among all the participants, 55.3% (47/85) and 28.2% (24/85) presented with LS/LS+ and LHON/LHON+, respectively. The median age at onset for LS/LS+ was significantly younger than that for LHON/LHON+ [median, (Q1–Q3), 3.0 (0.58–9.5) vs. 13.5 (5.75–41.75), P = 0.001]. A negative linear correlation was observed between mutation load and age of onset in patients who presented with LS/LS+ (R2 = 0.592, P < 0.001), with the age of onset ranging from infancy to adulthood. Patients with an older age at onset [OR (95% CI), 1.46 (1.12–1.91), P = 0.005] or higher mutation loads [OR (95% CI), 1.14 (1.03–1.26), P = 0.011] were more likely to present with LHON/LHON+ than with LS/LS+. A total of 17 patients were documented as having received a combination of mitochondrial cofactor treatments. Compared with patients with LHON/LHON+, patients with LS/LS+ exhibited an exceedingly high probability of a stable or worsen outcome (93.8% vs. 33.3%, P = 0.006). Conclusions LS/LS+ and LHON/LHON+ are the predominant presentations of the m.10197G>A mutation. An older age at onset and greater mutation load increases the probability of an LHON/LHON+ presentation. Patients presenting with LS/LS+ have an exceedingly high possibility of an unfavorable outcome. The identification of factors and outcomes associated with phenotypes in patients with the m.10197G>A mutation facilitates the provision of improved prognostic counseling for patients and their family members who are carriers of this mutation.https://doi.org/10.1186/s13023-025-03588-5ND3Leigh syndromeLeber hereditary optic neuropathyDystoniaMitochondrial disease |
| spellingShingle | YuZhi Shi Bin Chen SongTao Niu XinGao Wang ZaiQiang Zhang Clinical spectrum, treatment and outcomes of the m.10197G>A mutation in MT-ND3: a case report, systematic review and meta-analysis Orphanet Journal of Rare Diseases ND3 Leigh syndrome Leber hereditary optic neuropathy Dystonia Mitochondrial disease |
| title | Clinical spectrum, treatment and outcomes of the m.10197G>A mutation in MT-ND3: a case report, systematic review and meta-analysis |
| title_full | Clinical spectrum, treatment and outcomes of the m.10197G>A mutation in MT-ND3: a case report, systematic review and meta-analysis |
| title_fullStr | Clinical spectrum, treatment and outcomes of the m.10197G>A mutation in MT-ND3: a case report, systematic review and meta-analysis |
| title_full_unstemmed | Clinical spectrum, treatment and outcomes of the m.10197G>A mutation in MT-ND3: a case report, systematic review and meta-analysis |
| title_short | Clinical spectrum, treatment and outcomes of the m.10197G>A mutation in MT-ND3: a case report, systematic review and meta-analysis |
| title_sort | clinical spectrum treatment and outcomes of the m 10197g a mutation in mt nd3 a case report systematic review and meta analysis |
| topic | ND3 Leigh syndrome Leber hereditary optic neuropathy Dystonia Mitochondrial disease |
| url | https://doi.org/10.1186/s13023-025-03588-5 |
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