CGG expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy with neurological manifestations
-
Published:2020-11-25
Issue:1
Volume:8
Page:
-
ISSN:2051-5960
-
Container-title:Acta Neuropathologica Communications
-
language:en
-
Short-container-title:acta neuropathol commun
Author:
Ogasawara Masashi, Iida Aritoshi, Kumutpongpanich Theerawat, Ozaki Ayami, Oya Yasushi, Konishi Hirofumi, Nakamura Akinori, Abe Ryuta, Takai Hiroshi, Hanajima Ritsuko, Doi Hiroshi, Tanaka Fumiaki, Nakamura Hisayoshi, Nonaka Ikuya, Wang Zhaoxia, Hayashi Shinichiro, Noguchi Satoru, Nishino IchizoORCID
Abstract
AbstractOculopharyngodistal myopathy (OPDM) is a rare hereditary muscle disease characterized by progressive distal limb weakness, ptosis, ophthalmoplegia, bulbar muscle weakness and rimmed vacuoles on muscle biopsy. Recently, CGG repeat expansions in the noncoding regions of two genes, LRP12 and GIPC1, 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 NOTCH2NLC. We aimed to identify and to clinicopathologically characterize patients with OPDM who have CGG repeat expansions in NOTCH2NLC (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 NOTCH2NLC 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 NOTCH2NLC. 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 ± 1.6 nm 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 NOTCH2NLC.
Funder
Intramural Research Grant Japan Agency for Medical Research and Development Bone and Joint Injury Prevention and Rehabilitation Center, University of Michigan
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Neurology (clinical),Pathology and Forensic Medicine
Reference22 articles.
1. 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. Nat Genet 18:164–167. https://doi.org/10.1038/ng0298-164 2. Deng J, Yu J, Li P, Luan X, Cao L, Zhao J, Yu M, Zhang W, Lv H, Xie Z et al (2020) Expansion of GGC repeat in GIPC1 is associated with oculopharyngodistal myopathy. Am J Hum Genet 106:793–804. https://doi.org/10.1016/j.ajhg.2020.04.011 3. Durmus H, Laval SH, Deymeer F, Parman Y, Kiyan E, Gokyigiti M, Ertekin C, Ercan I, Solakoglu S, Karcagi V et al (2011) Oculopharyngodistal myopathy is a distinct entity: clinical and genetic features of 47 patients. Neurology 76:227–235. https://doi.org/10.1212/WNL.0b013e318207b043 4. Fang P, Yu Y, Yao S, Chen S, Zhu M, Chen Y, Zou K, Wang L, Wang H, Xin L et al (2020) Repeat expansion scanning of the NOTCH2NLC gene in patients with multiple system atrophy. Ann Clin Transl Neurol 7:517–526. https://doi.org/10.1002/acn3.51021 5. Hayashi T, Katagiri S, Mizobuchi K, Yoshitake K, Kameya S, Matsuura T, Iwata T, Nakano T (2020) Heterozygous GGC repeat expansion of NOTCH2NLC in a patient with neuronal intranuclear inclusion disease and progressive retinal dystrophy. Ophthal Genet 41:93–95. https://doi.org/10.1080/13816810.2020.1723119
Cited by
73 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|