CGG Repeat Expansion in GIPC1 is Associated with Childhood-Onset Hereditary Ataxia
Ying Wu1, Taoyun Ji1, Quanzhen Tan1
1Children's Medical Center, Peking University First Hospital, Beijing, China.
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.
