CGG Repeat Expansion in GIPC1 is Associated with Childhood-Onset Hereditary Ataxia.

BACKGROUND

Hereditary ataxias are genetically heterogeneous; however, despite major advances in next-generation sequencing technologies, 20%-54% of childhood-onset cases remain genetically undiagnosed.

OBJECTIVE

To elucidate the genetic etiology of childhood-onset hereditary ataxia.

METHODS

Oxford Nanopore long-read genome sequencing (LRS) was performed in two unrelated Chinese patients with clinically suspected childhood-onset hereditary ataxia.

RESULTS

Both patients presented with childhood-onset, slowly progressive ataxia, accompanied by mild cognitive impairment. Brain magnetic resonance imaging demonstrated cerebellar atrophy, and electromyography showed neurogenic damage. Muscle biopsy revealed fiber-type grouping, indicative of neurogenic changes, with no evidence of primary myopathy. LRS detected pathogenic-length CGG repeat expansions (>100 repeats) in GIPC1, which were validated by repeat-primed polymerase chain reaction.

CONCLUSIONS

These findings expand the phenotypic spectrum associated with GIPC1 CGG repeat expansion and define a novel subtype of childhood-onset hereditary ataxia accompanied by mild cognitive impairment and neurogenic involvement. © 2026 International Parkinson and Movement Disorder Society.