Intranuclear inclusions in muscle biopsy can differentiate oculopharyngodistal myopathy and oculopharyngeal muscular dystrophy

• Published in: Acta neuropathologica communications Vol. 10; no. 1; p. 176
• Main Authors: Ogasawara, Masashi, Eura, Nobuyuki, Iida, Aritoshi, Kumutpongpanich, Theerawat, Minami, Narihiro, Nonaka, Ikuya, Hayashi, Shinichiro, Noguchi, Satoru, Nishino, Ichizo
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 07.12.2022; BioMed Central; BMC
• Subjects: Biopsy; Biotechnology; Blood vessels; CGG repeat expansion; Comparative analysis; Computer industry; Disease; GIPC1; Histopathology; Humans; Immunohistochemistry; Intranuclear Inclusion Bodies; LRP12; Muscular dystrophy; Muscular Dystrophy, Oculopharyngeal - diagnosis; Mutation; NOTCH2NLC; Oculopharyngeal muscular dystrophy; Oculopharyngodistal myopathy; Pathology; Proteins; Statistical analysis; United States; United States > US; Japan; Oculopharyngodistal myopathy; GIPC1; Oculopharyngeal muscular dystrophy; Intranuclear inclusion; CGG repeat expansion; LRP12; NOTCH2NLC
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/s40478-022-01482-w

Oculopharyngodistal myopathy (OPDM) and oculopharyngeal muscular dystrophy (OPMD) are similar and even believed to be indistinguishable in terms of their myopathological features. To address the diagnostic gap, we evaluated the muscle biopsy samples for p62 expression by immunohistochemistry and compared the occurrence and the frequency of intranuclear inclusions among the individuals with OPDM (harboring CGG repeat expansion in LRP12 (n = 19), GIPC1 (n = 6), or NOTCH2NLC (n = 7)), OPMD (n = 15), and other rimmed vacuolar myopathies. We found that myonuclei with p62-positive intra-nuclear inclusions (myo-INIs) were significantly more frequent in OPMD (11.9 ± 1.1%, range 5.9-18.6%) than in OPDM and other rimmed vacuolar myopathies (RVMs) (0.9-1.5% on average, range 0.0-2.8%, p < 0.0001). In contrast, INIs in non-muscle cells such as blood vessels, peripheral nerve bundles, and muscle spindles (non-muscle-INIs) were present in OPDM, but absent in OPMD. These results indicate that OPMD can be differentiated from OPDM and other RVMs by the frequent presence of myo-INIs; and in OPDM, the presence of non-muscle-INIs in muscle pathology should be a diagnostic hallmark.