Identification and characterisation of a large Senataxin (SETX) gene duplication in ataxia with ocular apraxia type 2 (AOA2)

Autosomal recessive cerebellar ataxia with ocular apraxia type 2 (AOA2) is a neurodegenerative disorder characterised by early onset cerebellar ataxia, sensory-motor neuropathy and frequently increased levels of α-fetoprotein. We describe a male patient with a phenotype highly suggestive of AOA2, but only one point mutation found by sequencing of the SETX gene. Further analysis revealed a large out-of-frame tandem duplication, encompassing exons 7, 8, 9 and 10. This duplication event occurred obviously by unequal homologous recombination between AluY sequences. Gross SETX deletions or duplications might be an underestimated cause of AOA2.