Maternally inherited deafness and unusual phenotypic manifestations associated with A3243G mitochondrial DNA mutation

Area of Science:

• Genetics
• Neurology
• Mitochondrial Biology

Background:

• The mitochondrial DNA A3243G transition is a known pathogenic mutation.
• This mutation is frequently associated with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) phenotype.
• However, a wide spectrum of clinical presentations is documented.

Observation:

• A patient presented with generalized seizures at age 12, followed by bilateral hearing loss and fatigue.
• Maternal inheritance of hearing loss suggested a mitochondrial cause.
• Molecular analysis confirmed a heteroplasmic A3243G transition in mitochondrial DNA.

Findings:

• Muscle biopsy revealed ragged-red fibers in the proband, an unusual finding in deafness-associated mitochondrial disorders.
• The family exhibited hearing impairment across four generations.
• Fatal cerebral embolization and heart attack occurred in maternal relatives, while diabetes was notably absent.

Implications:

• This case highlights the diverse clinical manifestations of the A3243G mitochondrial DNA mutation.
• The presence of ragged-red fibers and absence of diabetes in this family broadens the understanding of this mutation's phenotypic variability.
• Further research is needed to elucidate the specific factors influencing the clinical spectrum of mitochondrial disorders.