Ataxia and oculomotor apraxia caused by a large-scale deletion in the senataxin gene.
Joanna M Rusecka, Biruta Kierdaszuk, Iwona Stępniak et al.
✦ AI-curated · Sources linked
Case in brief
Two adult patients developed cerebellar syndrome, scanned speech and exercise intolerance beginning in the second or third decade, followed by muscle weakness and impaired gait coordination. Whole-exome sequencing showed reduced coverage across an approximately 16-kb region of chromosome 9, indicating a homozygous deletion of SETX exons 11–15. The deletion causes a frameshift and truncation of the protein’s helicase domain. Given that SETX loss-of-function variants are pathogenic, the finding explained the patients’ presentation as SETX-related disease.
What made this case unusual
The causative finding was a large homozygous deletion spanning five SETX exons, detected through reduced sequencing coverage rather than identification of a single-nucleotide variant.
Diagnostic / clinical pearl
When sequencing data show reduced coverage across SETX in a patient with progressive cerebellar features, assess for a copy-number deletion as well as single-nucleotide variants.