{'fraction_non_alphanumeric': 0.042767732962447846, 'fraction_numerical': 0.02851182197496523, 'mean_word_length': 4.8121212121212125, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Assessment of GGC Repeat Expansion in GIPC1 in Patients with Parkinson's Disease

The cause of Parkinson’s disease (PD) is still unclear, and it is thought to be caused by a combination of aging, genetic and environmental risk factors. Mutations of more than 20 genes have been identified to cause PD. Short tandem repeat (STR) expansions have been found to be associated with PD (eg, CAG expansions in several spinocerebellar ataxia genes, the expanded GGC (A trinucleotide repeat GGC expansion) repeat in Notch 2 N-Terminal Like C gene (NOTCH2NLC)). In this study, we aimed to explore the role of tandem repeat expansions in the pathogenesis of PD. Initially, 85 unrelated Chinese patients with PD were performed with whole-genome long-read sequencing (LRS) on the Oxford Nanopore PromethION platform (see Appendix S1). Based on the STR detection with LRS data, we found two patients with PD (PD-1 and PD-2) harboring pathologic GGC repeat expansions (larger than 70 repeats) in the 50 untranslated region of PDZ domain containing family member 1 gene (GIPC1) (Fig. 1A,B), which was identified as a frequent cause of Oculopharyngodistal myopathy (OPDM). Repeat-primed polymerase chain reaction (RP-PCR) and GC-rich polymerase chain reaction (GC-PCR) were conducted to confirm the LRS results. The electropherogram demonstrated a sawtooth pattern in both cases, and the sizes of the detected expansion were 101 repeats and 85 repeats, respectively (Fig. 1C,D). Next, we screened GGC repeat expansion in GIPC1 in a larger cohort of 2419 unrelated patients with PD using RP-PCR and GC-PCR (Table S1). We found that another 16 sporadic patients with PD also carried expanded GGC repeats in GIPC1 (Fig. S1). Together, there were a total of 18 patients with PD who harbored GGC repeat expansions in GIPC1, and the GGC repeat sizes ranged from 70 to 401. A careful review of the clinical features of the patients carrying the pathogenic GIPC1 GGC expansion confirmed the diagnosis of PD, and none of them manifested any OPDM phenotype (Figs. S2 and S3, Table S2; see Appendix S1). Moreover, our study investigated the allelic distribution of GIPC1 GGC repeat in the healthy population. Intriguingly, eight of 1631 Chinese healthy control subjects also showed GIPC1 GGC repeat expansions (Fig. S4). Although the carrier rate of the pathogenic GIPC1 GGC repeat expansions was higher among patients with PD than that among healthy individuals (0.72% vs. 0.49%, respectively) (Fig. 1E), no significant difference was observed in the distribution of pathogenic GIPC1 GGC repeat between patients with PD and controls (Fisher’s exact test P value = 0.42; odds ratio, 1.46; 95% confidence interval, 0.6060–3.9136). In agreement with previously reported observations in OPDM, we did note that the incomplete penetrance was presented in the family with PD (Figs. S5 and S6). Our finding, for