Three separate recessive mutations (p.L52F, p.G77S, p.R105G) and a compound heterozygous mutation (c.295delT: p.Phe99Leufs*18 and c.334A >G:p.Ser112Gly) in ISCA2 have been reported to cause a mitochondrial syndrome known as “multiple mitochondrial dysfunctions syndrome 4” (OMIM#615317; MIM# 616370) characterized by leukodystrophy, optic atrophy, nystagmus, hypotonia with spasticity and neurodevelopmental. The functional impairment of the complex II and IV in muscle leads to the disease.
Prevalence
Unknown, limited to 21 reported cases, mostly from Saudi Arabian families, in the world.
Inheritance
Mutations of this gene can be passed on to the next generation in an autosomal recessive manner. This means that if both parents carry a mutation involving this gene (usually without displaying the disease), there is a greater chance that their children are going to inherit the mutations from both parents and display the disease. This is especially important to consider in consanguineous marriage, where the chance of both parents having the same mutation and passing it is greater.