Molecular characteristics
MFF (Mitochondrial Fission Factor) gene is located at 2q36.3 and encodes a protein that recruits dynamin-1-like protein to the mitochondrial surface and promotes mitochondrial and peroxisomal fission.
Mutations and pathophysiology
Mutations in MFF cause a dual fission defect in both mitochondria and peroxisomes. Fibroblasts from affected patients show a tubular appearance of the mitochondria and peroxisomes consistent with increased fusion and reduced fission. Fission defects are more consequential to mitochondria as compared with peroxisomes, as patients with MFF mutations did not display any apparent peroxisomal disturbance phenotype. Disturbing mitochondrial fission however produces the phenotype described in the Clinical Characteristics Section.
The following are some selected examples of the pathogenic variants in MFF:
Shamseldin et al. (2012) reported homozygosity for c.190C>T mutation in MFF leading to Q64X substitution, which is predicted to remove the transmembrane domain. The affected patients came from a consanguineous Saudi family.
Koch et al. (2016) reported a compound heterozygous mutation in MFF: c.184dup leading to frameshift and premature truncation of the protein (Leu62ProfsTer13) and c.892C>T leading to R298X substitution. The affected patient came from an Austrian family. A homozygous c.453_454del mutation leading to frameshift and premature truncation of the protein (Glu153AlafsTer5) was also identified. The affected patients came from a consanguineous Turkish family.