A comprehensive study of clinicopathological and genetic features of neuronal intranuclear inclusion disease

Minglei Liu^#¹, Yuan Gao^#^{1

2

3

4}, Yanpeng Yuan^{1

2

3

4}, Xiaojing Liu^{1

2

4}, Yangyang Wang^{1

2

4}, Lanjun Li^{1

2

4}, Xiaoyun Zhang¹, Chenyang Jiang^{1

3}, Qingzhi Wang¹, Yanlin Wang^{1

2

3

4}, Changhe Shi^{5

6}, Yuming Xu^{7

8

9

10}, Jing Yang^{11

12

13}

Affiliations

¹ Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China.
² NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, China.
³ Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China.
⁴ Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China.
⁵ Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China. shichanghe@gmail.com.
⁶ Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China. shichanghe@gmail.com.
⁷ Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China. xuyuming@zzu.edu.cn.
⁸ NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, China. xuyuming@zzu.edu.cn.
⁹ Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China. xuyuming@zzu.edu.cn.
¹⁰ Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China. xuyuming@zzu.edu.cn.
¹¹ Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China. yangjing9527@126.com.
¹² NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, China. yangjing9527@126.com.
¹³ Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China. yangjing9527@126.com.

^# Contributed equally.

PMID: 37184590
DOI: 10.1007/s10072-023-06845-2

A comprehensive study of clinicopathological and genetic features of neuronal intranuclear inclusion disease

Minglei Liu et al. Neurol Sci. 2023 Oct.

. 2023 Oct;44(10):3545-3556.

doi: 10.1007/s10072-023-06845-2. Epub 2023 May 15.

Authors

Affiliations

¹ Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China.
² NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, China.
³ Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China.
⁴ Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China.
⁵ Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China. shichanghe@gmail.com.
⁶ Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China. shichanghe@gmail.com.
⁷ Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China. xuyuming@zzu.edu.cn.
⁸ NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, China. xuyuming@zzu.edu.cn.
⁹ Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China. xuyuming@zzu.edu.cn.
¹⁰ Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China. xuyuming@zzu.edu.cn.
¹¹ Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China. yangjing9527@126.com.
¹² NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, China. yangjing9527@126.com.
¹³ Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China. yangjing9527@126.com.

^# Contributed equally.

PMID: 37184590
DOI: 10.1007/s10072-023-06845-2

Abstract

Background: The discovery of skin intranuclear inclusions and GGC repeat expansion of NOTCH2NLC has greatly promoted the diagnosis of neuronal intranuclear inclusion disease (NIID). With highly heterogeneous clinical manifestations, NIID patients tend to be underdiagnosed at early stages.

Methods: This study comprehensively studied clinical manifestations, magnetic resonance imaging (MRI), and peripheral nerve conduction in 24 NIID and 166 other neurodegenerative disease (ND) subjects. The nomogram was plotted using the "rms" package, and the t-distributed stochastic neighbor embedding algorithm was performed. Associations between skin intranuclear inclusions and NOTCH2NLC GGC repeats were further analyzed.

Results: The clinical, MRI, and peripheral nerve conduction features seriously overlapped in NIID and ND patients; they were assigned variables according to their frequency and specificity in NIID patients. A nomogram that could distinguish NIID from ND was constructed according to the assigned variables and cutoff values of the above features. The occurrence of skin intranuclear inclusions and NOTCH2NLC GGC repeats ≥ 60 showed 100% consistency, and intranuclear inclusion frequency positively correlated with NOTCH2NLC GGC repeats. A hierarchical diagnostic flowchart for definite NIID was further established.

Conclusion: We provide a novel nomogram with the potential to realize early identification and update the diagnostic flowchart for definitive diagnosis. Moreover, this is the first study to define the association between skin pathology and NOTCH2NLC genetics in NIID.

Keywords: Diagnostic flowchart; NOTCH2NLC; Neuronal intranuclear inclusion disease; Nomogram; Skin biopsy.

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References

1. Sone J, Mori K, Inagaki T, Katsumata R, Takagi S, Yokoi S, Araki K, Kato T, Nakamura T, Koike H, Takashima H, Hashiguchi A, Kohno Y, Kurashige T, Kuriyama M, Takiyama Y, Tsuchiya M, Kitagawa N, Kawamoto M, Yoshimura H, Suto Y, Nakayasu H, Uehara N, Sugiyama H, Takahashi M, Kokubun N, Konno T, Katsuno M, Tanaka F, Iwasaki Y, Yoshida M, Sobue G (2016) Clinicopathological features of adult-onset neuronal intranuclear inclusion disease. Brain 139(Pt 12):3170–3186 - PubMed - PMC - DOI
1. Lindenberg R, Rubinstein LJ, Herman MM, Haydon GB (1968) A light and electron microscopy study of an unusual widespread nuclear inclusion body disease. A possible residuum of an old herpesvirus infection. Acta Neuropathol. 10(1):54–73 - PubMed - DOI
1. Sone J, Tanaka F, Koike H, Inukai A, Katsuno M, Yoshida M, Watanabe H, Sobue G (2011) Skin biopsy is useful for the antemortem diagnosis of neuronal intranuclear inclusion disease. Neurology 76(16):1372–1376 - PubMed - DOI
1. Ishiura H, Shibata S, Yoshimura J, Suzuki Y, Qu W, Doi K, Almansour MA, Kikuchi JK, Taira M, Mitsui J, Takahashi Y, Ichikawa Y, Mano T, Iwata A, Harigaya Y, Matsukawa MK, Matsukawa T, Tanaka M, Shirota Y, Ohtomo R, Kowa H, Date H, Mitsue A, Hatsuta H, Morimoto S, Murayama S, Shiio Y, Saito Y, Mitsutake A, Kawai M, Sasaki T, Sugiyama Y, Hamada M, Ohtomo G, Terao Y, Nakazato Y, Takeda A, Sakiyama Y, Umeda-Kameyama Y, Shinmi J, Ogata K, Kohno Y, Lim SY, Tan AH, Shimizu J, Goto J, Nishino I, Toda T, Morishita S, Tsuji S (2019) Noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and an overlapping disease. Nat Genet. 51(8):1222–32 - PubMed - DOI
1. Sone J, Mitsuhashi S, Fujita A, Mizuguchi T, Hamanaka K, Mori K, Koike H, Hashiguchi A, Takashima H, Sugiyama H, Kohno Y, Takiyama Y, Maeda K, Doi H, Koyano S, Takeuchi H, Kawamoto M, Kohara N, Ando T, Ieda T, Kita Y, Kokubun N, Tsuboi Y, Katoh K, Kino Y, Katsuno M, Iwasaki Y, Yoshida M, Tanaka F, Suzuki IK, Frith MC, Matsumoto N, Sobue G (2019) Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC associated with neuronal intranuclear inclusion disease. Nat Genet 51(8):1215–21 - PubMed - DOI

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A comprehensive study of clinicopathological and genetic features of neuronal intranuclear inclusion disease

Affiliations

A comprehensive study of clinicopathological and genetic features of neuronal intranuclear inclusion disease

Authors

Affiliations

Abstract

References

MeSH terms

Supplementary concepts

Grants and funding

LinkOut - more resources

Full Text Sources

Medical