Intronic FDXR variant creates cryptic exon underlying fatal ataxia in Quarter Horses

Researchers including Briana N. Brown, Carrie J. Finno, and colleagues have published a study in PLOS Genetics describing the molecular basis of Equine Juvenile Spinocerebellar Ataxia (EJSCA), a recently characterised autosomal recessive neurological disease in Quarter Horses. Affected foals display progressive proprioceptive ataxia — impaired coordination and awareness of limb position — within one to five weeks of birth, deteriorating to recumbency and necessitating euthanasia.

Using whole-genome sequencing of seven affected cases and unaffected horses including obligate carriers, the team identified a causative intronic variant in the Ferredoxin Reductase gene (FDXR). The variant creates a cryptic exon — a previously silent stretch of intronic sequence that, when aberrantly incorporated into messenger RNA, disrupts normal protein production. FDXR encodes a mitochondrial enzyme involved in iron-sulphur cluster biosynthesis and electron transfer; loss of function has previously been linked to neurological disease in other species.

The discovery provides a molecular target for carrier testing in Quarter Horse breeding programmes and adds EJSCA to the growing catalogue of inherited equine neurological conditions with defined genetic causes. The finding is also of broader interest to researchers studying cryptic splice-site variants and mitochondrial disease mechanisms across species.