Oculopharyngeal myopathy with leukoencephalopathy (OPML) is a rare neurodegenerative disorder with autosomal dominant inheritance that was identified in 2019. To date, only three OPML patients have been described, and they are all from a single Japanese family (Ishiura et al., 2019). OPML is caused by a CGG/CCG repeat expansion in a gene (LOC642361/NUTM2B-AS1) on chromosome 10, from which long noncoding ribonucleic acid (RNA) is bidirectionally transcribed. Clinicopathological features of the three OPML patients include ptosis, restricted eye movement, dysphagia, dysarthria, diffuse limb muscle weakness, and nonspecific myopathic changes in muscle biopsy samples. Brain magnetic resonance imaging (MRI) revealed T2 hyperintensity signals in the white matter and brain atrophy, as well as dysfunction of multiple internal organs. However, it remains unknown whether their clinicopathological features are typical for CGG repeat expansions in LOC642361/NUTM2B-AS1. Thus, expanding the number of examined cases will improve our understanding of this disease and potentially help to understand the biomolecular details of how the repeat expansions in LOC642361/NUTM2B-AS1 drive its pathogenesis.

In this study, leveraging long read sequencing, we detail a case series comprising 12 patients from 3 unrelated families with CGG repeat expansions in LOC642361/NUTM2B-AS1. We identify the typical clinicopathological features and provide an initial insight into the disease mechanisms associated with LOC642361/NUTM2B-AS1-related disease.