A Heterozygous Mutation in MFF Associated with a Mild Mitochondrial Phenotype

Area of Science:

• Genetics
• Cell Biology
• Neurology

Background:

• Increasing number of nuclear gene mutations cause mitochondrial disease.
• Accurate diagnosis of neuromuscular disorders is crucial as symptoms can mimic acquired conditions.
• A novel heterozygous variant in mitochondrial fission factor (MFF) was identified, presenting symptoms similar to myasthenia gravis.

Purpose of the Study:

• To investigate if the MFF c.937G>A, p.E313K variant results in a mild mitochondrial phenotype.

Main Methods:

• Whole exome sequencing (WES) identified a novel heterozygous MFF variant in a patient with ptosis, fatigue, and muscle weakness.
• Patient-derived fibroblasts were utilized to assess mitochondrial and peroxisome dynamics.

Main Results:

• Fibroblasts from the patient exhibited impaired mitochondrial fission.
• Normal recruitment of Drp1 to mitochondria was observed despite the fission defect.

Conclusions:

• The MFF c.937G>A, p.E313K variant is associated with a mild mitochondrial phenotype.
• Defective mitochondrial fission in patient-derived fibroblasts is linked to this MFF variant.