GIPC1 CGG Repeat Expansion Is Associated with Movement Disorders

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Abstract
Objective: CGG/GGC repeat expansion in FMR1 and NOTCH2NLC is reportedly associated with movement disorders; therefore, we hypothesized that the CGG repeat expansion in LRP12, NUTM2B‐AS1, and GIPC1, which was previously identified in myopathy, might also be associated with movement‐disorder phenotypes. Here, we investigated whether CGG repeat expansion in LRP12, NUTM2B‐AS1, and GIPC1 presents in a cohort of patients with movement disorders.Methods: We screened for the CGG repeat expansion in LRP12, NUTM2B‐AS1, and GIPC1 in 1,346 movement‐disorder patients and 1,451 matched healthy controls.Results: No patients or controls harbored expanded CGG repeats in LRP12 or NUTM2B‐AS1, whereas 16 patients harbored >40 CGG repeats in GIPC1, with 11 of these patients harboring >60 CGG repeats. One control individual harbored an expanded GIPC1 allele (83 CGG units), suggesting that approximately 1% of patients affected by movement disorders in our population might harbor GIPC1 CGG repeat expansion, with this likely extremely rare in healthy controls (GIPC1 CGG repeat‐positive patients strongly resembled those in patients displaying NOTCH2NLC GGC repeat‐positive movement disorders. Additionally, the GIPC1 CGG repeat‐positive patients presented white‐matter hyperintensities but without typical NOTCH2NLC‐related high‐intensity signals in the corticomedullary junction. Furthermore, 44% of the GIPC1 CGG repeat‐positive patients showed a cognitive deficit, and skin biopsies in 2 patients revealed deposition of intranuclear inclusions.Interpretation: The CGG repeat expansion in GIPC1 might be associated with movement‐disorder phenotypes and lead to diseases related to intranuclear inclusions. ANN NEUROL 2022;91:704–715
Funding Information
  • National Key Research and Development Program of China (2017YFA0105000)
  • National Natural Science Foundation of China (81771290, 81974211, 82171247, 91849115, U1904207)

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