Mitochondrial fission factor gene mutation: A dilemma for prenatal diagnosis

Abstract

Mitochondrial fission factor (MFF) gene mutations are rare mitochondrial fission disorders, resulting in autosomal recessive neurological disorders. We here report a rare case of MFF gene mutation running in a family which ultimately turned out to be a variant of unknown significance. A 29-year-old multigravida visited at 18-week gestation for prenatal genetic testing as her previous baby had cerebral palsy and global developmental delay. The exome sequencing of the affected baby revealed defective mitochondrial and peroxisomal fission 2 (AR-617086). On Sanger sequencing, the mother was homozygous and the father heterozygous for the same variant. In the current pregnancy, amniocentesis was done and the fetus was also homozygous for a similar mutation. The couple continued the pregnancy and delivered a healthy baby who had normal milestones at 11 months of age. As far as prenatal diagnostic testing is considered, our case is a real-world scenario, where patient expectations befuddle appropriate decision-making.

Systemic phospho-defective and phospho-mimetic Drp1 mice exhibit normal growth and development with altered anxiety-like behavior

“…Finally, mutations in Drp1 and its receptor Mff lead to human conditions characterized by neurodevelopmental defects, microcephaly, refractory epilepsy, hypotonia, ataxia, seizures, and optic atrophy. 63 , 64 , 65 , 66 , 67 , 68 Therefore, it is crucial to decipher the regulation of Drp1-mediated mitochondrial division and translate this fundamental knowledge into therapeutic interventions to treat mitochondrial division-associated diseases and improve human health.…”

Fission Impossible (?)—New Insights into Disorders of Peroxisome Dynamics

“…Several patients with MFF deficiency, a rare autosomal recessive neurological disorder (OMIM#617086), have been identified. This is caused by various mutations in the MFF gene, all of which (except one) lead to a truncated protein lacking the C-terminal TMD and tail ( Appendix A ) [c.C190T:p.Q64* [ 119 ]; c.184dup:p.L62Pfs*13 combined with c.C892T:p.R298* [ 120 ]; c.453_454del:p.E153Afs*5 [ 120 ]); c.C892T:p.R298* [ 121 ]; c.C433T:p.R145* [ 122 ]; c.19_20delAGinsTT:p.S7F [ 123 ]]. MFF truncations with a loss of the C-terminal TMD and tail will abolish the targeting and membrane localization of MFF, resulting in its absence at mitochondria and peroxisomes.…”

“…Those patients show neurological abnormalities with onset during the first year of life and may present with Leigh-like encephalopathy, developmental delay, peripheral neuropathy, optic atrophy, and microcephaly [ 119 , 120 , 121 , 122 ]. A recent case with an amino acid change from serine to phenylalanine at position 7 was reported [ 123 ]. The 5-year-old male patient presented with cerebral palsy and encephalopathy, but without seizures or vision abnormality.…”