The relationship between MFF and Leigh syndrome spectrum was evaluated using the ClinGen Clinical Validity Framework as of September 21, 2020. The MFF gene encodes mitochondrial fission factor, which plays an important role in mitochondrial fission. Mitochondria are dynamic organelles constantly moving along the cell cytoskeleton and form functional networks in many cells. Mitochondria undergo frequent fusion and fission events, which allow formation of these networks. Defects in MFF lead to abnormal mitochondrial morphology and dynamics.
The MFF gene was first reported in relation to autosomal recessive Leigh syndrome spectrum in 2016 (PMID: 26783368). Evidence supporting this gene-disease relationship includes case-level data and experimental data. This curation included five variants identified in four cases in three publications (PMIDs: 26783368, 30581454, 32181496). No segregation data were available. Loss of function is implicated as the mechanism of disease. This gene-disease association is also supported by known biochemical function, expression, and functional alteration in patient cells (PMIDs: 27977873, 25613900, 26783368).
In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the NICHD U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel on September 21, 2020 (SOP Version 7).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.