The Value of NOTCH2NLC Gene Detection and Skin Biopsy in the Diagnosis of Neuronal Intranuclear Inclusion Disease
The clinical manifestations of neuronal intranuclear inclusion disease (NIID) are heterogeneous, and the premortem diagnosis is mainly based on skin biopsy findings. Abnormal GGC repeat expansions in NOTCH2NLC was recently identified in familial and sporadic NIID. The comparison of diagnostic value...
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2021.624321/full |
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| author | Jie Pang Jie Pang Jing Yang Jing Yang Jing Yang Yanpeng Yuan Yanpeng Yuan Yuan Gao Yuan Gao Yuan Gao Changhe Shi Changhe Shi Shiheng Fan Shiheng Fan Yuming Xu Yuming Xu Yuming Xu |
| author_facet | Jie Pang Jie Pang Jing Yang Jing Yang Jing Yang Yanpeng Yuan Yanpeng Yuan Yuan Gao Yuan Gao Yuan Gao Changhe Shi Changhe Shi Shiheng Fan Shiheng Fan Yuming Xu Yuming Xu Yuming Xu |
| author_sort | Jie Pang |
| collection | DOAJ |
| description | The clinical manifestations of neuronal intranuclear inclusion disease (NIID) are heterogeneous, and the premortem diagnosis is mainly based on skin biopsy findings. Abnormal GGC repeat expansions in NOTCH2NLC was recently identified in familial and sporadic NIID. The comparison of diagnostic value between abnormal GGC repeat expansions of NOTCH2NLC and skin biopsy has not been conducted yet. In this study, skin biopsy was performed in 10 suspected adult NIID patients with clinical and imaging manifestations, and GGC repeat size in NOTCH2NLC was also screened by repeat primed-PCR and GC-rich PCR. We found that five cases had ubiquitin-immunolabelling intranuclear inclusion bodies by skin biopsy, and all of them were identified with abnormal GGC repeat expansions in NOTCH2NLC, among whom four patients showed typical linear hyperintensity at corticomedullary junction on DWI. Five (5/10) NIID patients were diagnosed by combination of NOTCH2NLC gene detection, skin biopsy or combination of NOTCH2NLC, and typical MRI findings. The diagnostic performance of NOTCH2NLC gene detection was highly consistent with that of skin biopsy (Kappa = 1). The unexplained headache was firstly reported as a new early phenotype of NIID. These findings indicate that NOTCH2NLC gene detection is needed to be a supplement in the diagnose flow of NIID and also may be used as an alternative method to skin biopsy especially in Asian population. |
| first_indexed | 2024-12-17T00:00:49Z |
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| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-17T00:00:49Z |
| publishDate | 2021-05-01 |
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| series | Frontiers in Neurology |
| spelling | doaj.art-9b3428b9e991405185aeddabdd2e076f2022-12-21T22:11:04ZengFrontiers Media S.A.Frontiers in Neurology1664-22952021-05-011210.3389/fneur.2021.624321624321The Value of NOTCH2NLC Gene Detection and Skin Biopsy in the Diagnosis of Neuronal Intranuclear Inclusion DiseaseJie Pang0Jie Pang1Jing Yang2Jing Yang3Jing Yang4Yanpeng Yuan5Yanpeng Yuan6Yuan Gao7Yuan Gao8Yuan Gao9Changhe Shi10Changhe Shi11Shiheng Fan12Shiheng Fan13Yuming Xu14Yuming Xu15Yuming Xu16Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaInstitute of Neuroscience, Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaInstitute of Neuroscience, Zhengzhou University, Zhengzhou, ChinaNational Health Commission Key Laboratory of Cerebrovascular Disease, Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaInstitute of Neuroscience, Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaInstitute of Neuroscience, Zhengzhou University, Zhengzhou, ChinaNational Health Commission Key Laboratory of Cerebrovascular Disease, Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaInstitute of Neuroscience, Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaInstitute of Neuroscience, Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaInstitute of Neuroscience, Zhengzhou University, Zhengzhou, ChinaNational Health Commission Key Laboratory of Cerebrovascular Disease, Zhengzhou University, Zhengzhou, ChinaThe clinical manifestations of neuronal intranuclear inclusion disease (NIID) are heterogeneous, and the premortem diagnosis is mainly based on skin biopsy findings. Abnormal GGC repeat expansions in NOTCH2NLC was recently identified in familial and sporadic NIID. The comparison of diagnostic value between abnormal GGC repeat expansions of NOTCH2NLC and skin biopsy has not been conducted yet. In this study, skin biopsy was performed in 10 suspected adult NIID patients with clinical and imaging manifestations, and GGC repeat size in NOTCH2NLC was also screened by repeat primed-PCR and GC-rich PCR. We found that five cases had ubiquitin-immunolabelling intranuclear inclusion bodies by skin biopsy, and all of them were identified with abnormal GGC repeat expansions in NOTCH2NLC, among whom four patients showed typical linear hyperintensity at corticomedullary junction on DWI. Five (5/10) NIID patients were diagnosed by combination of NOTCH2NLC gene detection, skin biopsy or combination of NOTCH2NLC, and typical MRI findings. The diagnostic performance of NOTCH2NLC gene detection was highly consistent with that of skin biopsy (Kappa = 1). The unexplained headache was firstly reported as a new early phenotype of NIID. These findings indicate that NOTCH2NLC gene detection is needed to be a supplement in the diagnose flow of NIID and also may be used as an alternative method to skin biopsy especially in Asian population.https://www.frontiersin.org/articles/10.3389/fneur.2021.624321/fullgeneleukoencephalopathyheadachenuclear inclusion bodiesskin biopsy |
| spellingShingle | Jie Pang Jie Pang Jing Yang Jing Yang Jing Yang Yanpeng Yuan Yanpeng Yuan Yuan Gao Yuan Gao Yuan Gao Changhe Shi Changhe Shi Shiheng Fan Shiheng Fan Yuming Xu Yuming Xu Yuming Xu The Value of NOTCH2NLC Gene Detection and Skin Biopsy in the Diagnosis of Neuronal Intranuclear Inclusion Disease Frontiers in Neurology gene leukoencephalopathy headache nuclear inclusion bodies skin biopsy |
| title | The Value of NOTCH2NLC Gene Detection and Skin Biopsy in the Diagnosis of Neuronal Intranuclear Inclusion Disease |
| title_full | The Value of NOTCH2NLC Gene Detection and Skin Biopsy in the Diagnosis of Neuronal Intranuclear Inclusion Disease |
| title_fullStr | The Value of NOTCH2NLC Gene Detection and Skin Biopsy in the Diagnosis of Neuronal Intranuclear Inclusion Disease |
| title_full_unstemmed | The Value of NOTCH2NLC Gene Detection and Skin Biopsy in the Diagnosis of Neuronal Intranuclear Inclusion Disease |
| title_short | The Value of NOTCH2NLC Gene Detection and Skin Biopsy in the Diagnosis of Neuronal Intranuclear Inclusion Disease |
| title_sort | value of notch2nlc gene detection and skin biopsy in the diagnosis of neuronal intranuclear inclusion disease |
| topic | gene leukoencephalopathy headache nuclear inclusion bodies skin biopsy |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2021.624321/full |
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