Washington: Researchers have identified a novel gene mutation that causes rare but devastating genetic diseases known as mitochondrial disorders.
Nine rare disease-causing mutations of the gene, FBXL4, were found in nine affected children in seven families, including three siblings from the same family, an international team of researchers reported in the American Journal of Human Genetics.
Mitochondrial diseases are caused by mutations in either mitochondrial DNA or in genes in the nucleus that encode for proteins that function in the mitochondria. Mitochondrial DNA is inherited from the mother.
Thus, a child can inherit a mitochondrial disease either from the mother alone or from both parents carrying mutations in the same nuclear gene.
FBXL4 is a nuclear gene that encodes for a protein called F-Box and Leucine-Rich Repeat Protein 4.
The study found that mutations of this gene lead to either truncated or altered forms of the protein.
These results in cells having less mitochondrial DNA, decreased mitochondrial membrane potential and a faulty process in cell metabolism called oxidative phosphorylation.
The study also proved that the FBXL4 protein is located exclusively in mitochondria, which was previously unrecognised.
The lead author of the study is Xiaowu Gai, director of the Center for Biomedical Informatics at Loyola University Chicago Stritch School of Medicine.
The discovery began with an 8-year-old girl who had a mitochondrial disease known as Leigh syndrome.
A battery of genetic tests of the girl and her parents over the years had failed to find any of the gene mutations previously known to cause mitochondrial diseases.
Gai and colleagues used the high-performance computer cluster to analyse billions of DNA sequences to identify the gene mutation in the child and her parents.
The research team then reached out to other collaborators to see if any of their patients also had the FBXL4 mutation.
Eight additional affected children in six unrelated families were found to also have disease-causing mutations in this gene.