The genetic cause of a rare and fatal form of mitochondrial disease has been uncovered by international researchers and published in the American Journal of Human Genetics.
Mitochondria are the power-generating structures of human cells; mutations in nuclear genes or the small number of mitochondrial genes in DNA located outside the cell nucleus can cause disease, ranging in severity from mild to very severe.
In this case, researchers examined DNA from affected individuals (two of whom died before the age of two) from three unrelated families of Arabian origin who had shown apparently very similar disease symptoms and progression. Exome sequencing revealed that the children had different mutations in the same gene, FBXL4, with severe effects on mitochondrial function.
Report author Penelope E. Bonnen from Baylor College of Medicine observed: “The number one reason a child is referred to a genetic clinic is developmental delay, which is often part of mitochondrial disease…It is important for us to be able to accurately diagnose children who have a mitochondrial disease and exclude those children who do not”.
Comment: Proposed new regulations that would permit the use of donor egg cells along with those of a woman carrying mitochondrial mutations in IVF (so-called three-parent IVF) are currently in development in the UK (see previous news). Approval of this technique would not help the families in this study conceive unaffected children, since the FBXL4 gene is in the nucleus. However, the new finding provides a definitive diagnosis of mitochondrial disease for the affected families and would allow prenatal testing to determine whether a foetus was affected.