Phenotypic Heterogeneity of the Mitochondrial DNA Variant m.13513 G > A

Area of Science:

• Genetics
• Mitochondrial Biology
• Neurology

Background:

• The mitochondrial DNA (mtDNA) variant m.13513G>A is a known cause of mitochondrial disorders (MIDs).
• Phenotypic variability associated with this variant necessitates a comprehensive understanding for accurate diagnosis and management.

Purpose of the Study:

• To review and synthesize recent and historical findings on the phenotypic heterogeneity of the mtDNA variant m.13513G>A.
• To consolidate information on patient demographics, clinical presentations, and outcomes associated with this variant.

Main Methods:

• A systematic literature review was conducted using PubMed and Google Scholar.
• Search terms focused on the mtDNA variant m.13513G>A and associated mitochondrial disorders.
• Data from at least 50 reported patients were analyzed as of July 2021.

Main Results:

• The mtDNA variant m.13513G>A presents with highly variable phenotypes, commonly including Leigh syndrome (LS) and mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).
• Reported cases (n=50) ranged in age from 0 to 63 years, with varying heteroplasmy levels (0-86%) across tissues.
• Overlapping syndromes like MELAS/LS and rare nonsyndromic presentations were also observed, with worse outcomes noted in LS patients.

Conclusions:

• The mtDNA variant m.13513G>A is a significant cause of both syndromic and nonsyndromic mitochondrial disorders.
• LS, MELAS, and Leber's hereditary optic neuropathy (LHON) are key syndromic MIDs to consider when this variant is present.
• Comprehensive mtDNA sequencing is recommended for patients with suspected MIDs and maternal inheritance to identify this and other rare variants.