Protein-bound iron-sulphur clusters are important biological cofactors and play a crucial role in electron transfer reactions. Additionally, they fulfill essential functions in diverse cellular pathways from catalysis of biochemical reactions to regulation of gene expression. Formation of these iron-sulphur clusters in mitochondria and cytosol and their assembly onto proteins is a complex process and consists of several stages. Defects in a number of genes involved in this process have been identified as the underlying causes of neurodegenerative diseases like, for example, Friedreich ataxia.

One of the protein classes that are essential for cluster assembly are ferredoxins. With FDX1 and FDX2, humans possess two ferredoxins. In a new study, researchers have now for the first time identified a homozygous missense mutation in FDX2 as the genetic cause of a novel, early-onset multisystemic disease in six patients from two Brazilian families. The patients presented with a phenotype involving optic atrophy, reversible leukoencephalopathy, mitochondrial myopathy with exercise intolerance and axonal polyneuropathy as well as, in some cases, pyramidal signs.

The results of this study have been published in Brain.

Gurgel-Giannetti J, Lynch DS, Paiva ARB, […] Kok F. A novel complex neurological phenotype due to a homozygous mutation in FDX2. Brain. 2018 Jul 13. doi: 10.1093/brain/awy172. [Epub ahead of print]