Expansion of 5' UTR CGG repeat in RILPL1 is associated with oculopharyngodistal myopathy

Oculopharyngodistal myopathy is an adult-onset degenerative muscle disorder characterized by ptosis, ophthalmoplegia and weakness of the facial, pharyngeal and limb muscles. Trinucleotide repeat expansions in non-coding regions of LRP12, G1PC1and NOTCH2NLC were recently reported to be the etiologies for OPDM. However, a significant portion of OPDM patients still have unknown genetic causes. In this study, we performed long-read whole-genome sequencing in a large five-generation family of 156 individuals, including 22 patients diagnosed with typical OPDM and identified CGG repeat expansions in RILPL1 gene in all patients we tested while not in unaffected family members. Methylation analysis indicated that methylation levels of the RILPL1 gene were unaltered in OPDM patients, which was in consistent with previous reports. Our findings first provided evidences that RILPL1 were associated OPDM which we suggested as OPDM type 4.