Heterozygous deletion of KLHL1/ATX8OS at the SCA8 locus is unlikely associated with cerebellar impairment in humans

Spinocerebellar ataxia type 8 is a dominantly inherited ataxia, mainly occurring in adulthood. It is caused by a CTG.CAG tract expansion in the ATXN8OS gene, an untranslated antisense transcript that partially overlaps the KLHL1 gene. We report two families, each composed of one parent and one son/daughter, segregating a small genomic deletion spanning only ATXN8OS gene and part of KLHL1. Both probands were referred for speech and articulation difficulties, and one had mild intellectual disability. The deletion was inherited from a healthy parent. Neither of the probands had signs of cerebellar dysfunction. MRI performed on two subjects of family 1 did not show brain anomalies. In contrast with the KLHL1/ATX8OS knockout mouse model, our data suggests that heterozygous deletion in KLHL1/ATX8OS is unlikely to be associated with ataxia/cerebellar involvement in humans, although it may contribute to speech/articulation problems or neuropsychiatric symptoms other than cerebellar/ataxia.