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Background <p>A correlation between various sites or types of mutations in mitochondrial DNA <i>ND3</i> and the development of a specific mitochondrial disease or phenotype has yet to be fully established.</p> Methods <p>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&gt;A mutation in <i>ND3</i>. A review of the literature was conducted to investigate the clinical spectrum, treatment and outcome resulting from the m.10197G&gt;A mutation. Phenotypes associated with the m.10197G&gt;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.</p> Results <p>A total of 84 participants (78 patients and 6 asymptomatic carriers) with the m.10197G&gt;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), <i>P</i> = 0.001]. A negative linear correlation was observed between mutation load and age of onset in patients who presented with LS/LS+ (R<sup>2</sup> = 0.592, <i>P</i> &lt; 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), <i>P</i> = 0.005] or higher mutation loads [OR (95% CI), 1.14 (1.03–1.26), <i>P</i> = 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%, <i>P</i> = 0.006).</p> Conclusions <p>LS/LS+ and LHON/LHON+ are the predominant presentations of the m.10197G&gt;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&gt;A mutation facilitates the provision of improved prognostic counseling for patients and their family members who are carriers of this mutation.</p>

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Clinical spectrum, treatment and outcomes of the m.10197G>A mutation in MT-ND3: a case report, systematic review and meta-analysis

  • 期刊论文

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  • 发表日期：

    2025年2月8日

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  • YuZhi Shi,
  • Bin Chen,
  • SongTao Niu,
  • XinGao Wang,
  • ZaiQiang Zhang

摘要

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.