Intranuclear inclusions in skin biopsies are not limited to neuronal intranuclear inclusion disease but can also be seen in oculopharyngodistal myopathy

Masashi Ogasawara; Nobuyuki Eura; Utako Nagaoka; Tatsuro Sato; Hajime Arahata; Tomohiro Hayashi; Tomoko Okamoto; Yuji Takahashi; Madoka Mori-Yoshimura; Yasushi Oya; Akinori Nakamura; Rui Shimazaki; Terunori Sano; Theerawat Kumutpongpanich; Narihiro Minami; Shinichiro Hayashi; Satoru Noguchi; Aritoshi Iida; Masaki Takao; Ichizo Nishino

doi:10.1111/nan.12787

Intranuclear inclusions in skin biopsies are not limited to neuronal intranuclear inclusion disease but can also be seen in oculopharyngodistal myopathy

Neuropathol Appl Neurobiol. 2022 Apr;48(3):e12787. doi: 10.1111/nan.12787. Epub 2021 Dec 28.

Authors

Masashi Ogasawara^{1

2}, Nobuyuki Eura^{1

2

3}, Utako Nagaoka⁴, Tatsuro Sato⁵, Hajime Arahata⁶, Tomohiro Hayashi⁷, Tomoko Okamoto⁸, Yuji Takahashi⁸, Madoka Mori-Yoshimura⁸, Yasushi Oya⁸, Akinori Nakamura⁹, Rui Shimazaki⁴, Terunori Sano¹⁰, Theerawat Kumutpongpanich¹, Narihiro Minami^{1

2}, Shinichiro Hayashi^{1

2}, Satoru Noguchi^{1

2}, Aritoshi Iida², Masaki Takao¹⁰, Ichizo Nishino^{1

2}

Affiliations

¹ Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Japan.
² Medical Genome Center, NCNP, Kodaira, Japan.
³ Department of Neurology, Nara Medical University, Nara, Japan.
⁴ Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan.
⁵ Department of Neurology, Hakodate Medical Association Hospital, Hakodate, Japan.
⁶ Department of Neurology, National Hospital Organization Omuta National Hospital, Omuta, Japan.
⁷ Department of Neurology, Toyama University Hospital, Toyama, Japan.
⁸ Department of Neurology, National Center Hospital, NCNP, Tokyo, Japan.
⁹ Department of Clinical Research, National Hospital Organization Matsumoto Medical Center, Matsumoto, Japan.
¹⁰ Department of Laboratory Medicine, NCNP, Kodaira, Japan.

PMID: 34927285
DOI: 10.1111/nan.12787

Abstract

Aims: Oculopharyngodistal myopathy (OPDM) is caused by the expansion of CGG repeats in NOTCH2NLC (OPDM_NOTCH2NLC) GIPC1 (OPDM_GIPC1), or LRP12 (OPDM_LRP12). Neuronal intranuclear inclusion disease (NIID) is clinically distinct from OPDM but is also caused by the expansion of CGG repeats in NOTCH2NLC, which may be an indicator of intranuclear inclusion in skin biopsy. We investigated the presence of intranuclear inclusions in skin biopsies from patients with OPDM and muscle diseases with a similar pathology to evaluate whether they will have similar diagnostic findings on skin biopsy.

Methods: We analysed the frequency of p62-positive intranuclear inclusions in sweat gland cells, adipocytes and fibroblasts in skin biopsy samples from patients with OPDM (OPDM_NOTCH2NLC [n = 2], OPDM_GIPC1 [n = 6] and OPDM_LRP12 [n = 3]), NIID (n = 1), OPMD (n = 1), IBM (n = 4) and GNE myopathy (n = 2).

Results: The p62-postive intranuclear inclusions were observed in all three cell types in both patients with OPDM_NOTCH2NLC and a patient with NIID, in at least one cell type in all six patients with OPDM_GIPC1, and all in three cell types in one of the three patients with OPDM_LRP12. These findings were not observed in patients with OPMD, IBM or GNE myopathy.

Conclusion: Intranuclear inclusions in skin biopsy samples are not specific to NIID and are found in all three types of genetically confirmed OPDM, suggesting that the underlying mechanism of OPDM may be similar to NIID, regardless of causative genes.

Keywords: CGG repeat expansion; GIPC1; LRP12; NOTCH2NLC; neuronal intranuclear inclusion disease; oculopharyngeal muscular dystrophy; oculopharyngodistal myopathy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biopsy
Humans
Intranuclear Inclusion Bodies* / pathology
Muscular Dystrophies* / genetics
Neurodegenerative Diseases

Supplementary concepts

Neuronal intranuclear inclusion disease
Oculopharyngodistal Myopathy