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Recently, CGG repeat expansions in the noncoding regions of two genes,\n                    <jats:italic>LRP12<\/jats:italic>\n                    and\n                    <jats:italic>GIPC1<\/jats:italic>\n                    , have been reported to be causative for OPDM. Furthermore, neuronal intranuclear inclusion disease (NIID) has been recently reported to be caused by CGG repeat expansions in\n                    <jats:italic>NOTCH2NLC<\/jats:italic>\n                    . We aimed to identify and to clinicopathologically characterize patients with OPDM who have CGG repeat expansions in\n                    <jats:italic>NOTCH2NLC<\/jats:italic>\n                    (OPDM_NOTCH2NLC). Note that 211 patients from 201 families, who were clinically or clinicopathologically diagnosed with OPDM or oculopharyngeal muscular dystrophy, were screened for CGG expansions in\n                    <jats:italic>NOTCH2NLC<\/jats:italic>\n                    by repeat primed-PCR. Clinical information and muscle pathology slides of identified patients with OPDM_NOTCH2NLC were re-reviewed. Intra-myonuclear inclusions were evaluated using immunohistochemistry and electron microscopy (EM). Seven Japanese OPDM patients had CGG repeat expansions in\n                    <jats:italic>NOTCH2NLC<\/jats:italic>\n                    . All seven patients clinically demonstrated ptosis, ophthalmoplegia, dysarthria and muscle weakness; they myopathologically had intra-myonuclear inclusions stained with anti-poly-ubiquitinated proteins, anti-SUMO1 and anti-p62 antibodies, which were diagnostic of NIID (typically on skin biopsy), in addition to rimmed vacuoles. The sample for EM was available only from one patient, which demonstrated intranuclear inclusions of 12.6\u2009\u00b1\u20091.6\u00a0nm in diameter. We identified seven patients with OPDM_NOTCH2NLC. Our patients had various additional central and\/or peripheral nervous system involvement, although all were clinicopathologically compatible; thus, they were diagnosed as having OPDM and expanding a phenotype of the neuromyodegenerative disease caused by CGG repeat expansions in\n                    <jats:italic>NOTCH2NLC<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1186\/s40478-020-01084-4","type":"journal-article","created":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T08:03:07Z","timestamp":1606291387000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":110,"title":["CGG expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy with neurological manifestations"],"prefix":"10.1186","volume":"8","author":[{"given":"Masashi","family":"Ogasawara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aritoshi","family":"Iida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theerawat","family":"Kumutpongpanich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayami","family":"Ozaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Oya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Konishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuta","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Takai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritsuko","family":"Hanajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Doi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiaki","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisayoshi","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuya","family":"Nonaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Noguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9452-112X","authenticated-orcid":false,"given":"Ichizo","family":"Nishino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,25]]},"reference":[{"key":"1084_CR1","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1038\/ng0298-164","volume":"18","author":"B Brais","year":"1998","unstructured":"Brais B, Bouchard JP, Xie YG, Rochefort DL, Chretien N, Tome FM, Lafreniere RG, Rommens JM, Uyama E, Nohira O et al (1998) Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy. 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This study was approved by the ethical committees of the NCNP (A2019-123).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors report no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"For patients with CGG expansions in <i>NOTCH2NLC<\/i>, clinical information that included imaging data of muscle and brain provided by the physicians at the time of muscle biopsy and\/or genetic analysis was reviewed.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Clinical information"}}],"article-number":"204"}}