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Published January 2023 | public
Journal Article

A Heterozygous Mutation in MFF Associated with a Mild Mitochondrial Phenotype

Abstract

Background: The number of mutations in nuclear encoded genes causing mitochondrial disease is ever increasing. Identification of these mutations is particularly important in the diagnosis of neuromuscular disorders as their presentation may mimic other acquired disorders. We present a novel heterozygous variant in mitochondrial fission factor (MFF) which mimics myasthenia gravis. Objective: To determine if the MFF c.937G>A, p.E313K variant causes a mild mitochondrial phenotype. Methods: We used whole exome sequencing (WES) to identify a novel heterozygous variant in MFF in a patient with ptosis, fatigue and muscle weakness. Using patient derived fibroblasts, we performed assays to evaluate mitochondrial and peroxisome dynamics. Results: We show that fibroblasts derived from this patient are defective in mitochondrial fission, despite normal recruitment of Drp1 to the mitochondria. Conclusions: The MFF c.937G>A, p.E313K variant leads to a mild mitochondrial phenotype and is associated with defective mitochondrial fission in patient-derived fibroblasts.

Additional Information

This work was made possible, in part, through philanthropic support from Dr. Peter Buck and additional anonymous contributors. CG and AS were supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke. We would like to thank the NIH Intramural Sequencing Center (NISC) for whole-exome sequencing and Elizabeth Hartnett, MSW, who contributed as the patient care coordinator for the NIH neurogenetics clinic. MI is supported through NIH grant GM131768. HS is supported through NIH grant GM144103 and also support from the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation. DC is supported through NIH R35 GM127147.

Additional details

Created:
August 22, 2023
Modified:
December 22, 2023