Abstract Details

Recently, CGG repeat expansions in LRP12, GIPC1, and RILPL1 genes have been found to be associated with oculopharyngodistal myopathy (OPDM), which provides insight into various undiagnosed neurodegenerative disorders. 

We collected DNA samples from 2,424 unrelated Japanese patients with IPN and selected 1,555 unidentified cases after conducting a series of prescreening analyses. Together with eight patients diagnosed with OPDM, we screened for CGG repeat expansions in LRP12, GIPC1, and RILPL1 genes using repeat-primed polymerase chain reaction (PCR), fluorescence amplicon length analysis-PCR, and long-read sequencing technologies. We summarized the clinical, electrophysiological, radiological, and pathological features of patients with disease-causing CGG repeat expansions.

Within the IPN group, LRP12 CGG repeat expansions were identified in 44 cases (LRP12-IPN), which was the fourth most common etiology in this case series. Most cases (29/37) developed only distal limb weakness without ptosis, ophthalmoplegia, facial muscle weakness, or bulbar palsy. Neurogenic changes were commonly observed using needle electromyography (97%) and skeletal muscle biopsy (100%). The number of LRP12 CGG repeat extensions of LRP12-IPN was less than that of three LRP12-OPDM patients (76.41 ± 17.97 vs. 127.00 ± 22.87 ; p = 0.0013). Additionally, we observed selective atrophy in lower limb flexor muscles and p62-positive inclusions in skeletal muscle and peripheral nerve samples regardless of the clinical phenotype. No CGG repeat expansion was detected in GIPC1 and RILPL1.