Effect of NOTCH2NLC Gene Variations on NIID Clinical Features (NOTCH2NLC-NIID)
This study aims to understand how differences in the NOTCH2NLC gene affect the symptoms and course of neuronal intranuclear inclusion disease (NIID), a rare inherited neurological disorder. NIID is caused by an abnormal expansion of a GGC DNA repeat in the NOTCH2NLC gene, but members of the same family can have very different repeat sizes and patterns, leading to a wide variety of problems-such as difficulties with memory, movement, sensation, or involuntary body functions. The main goal is to uncover how these genetic differences (repeat length and interruption pattern) contribute to the severity and type of symptoms.
The study is being conducted at Sichuan Provincial People's Hospital and will enroll approximately 12 individuals from a single family, including those diagnosed with NIID, family members who carry the genetic change but are not yet sick, and healthy relatives. Participants must be 18-85 years old, able to complete genetic testing and a small skin biopsy, and willing to provide informed consent. Those who are medically unstable or otherwise unable to participate will not be enrolled.
The study has both a retrospective part (collecting past medical records) and a prospective follow-up. At the beginning, all participants will have a physical exam, provide a blood sample (for long-read DNA sequencing and RNA sequencing), and undergo a 3-mm skin biopsy to look for disease-related protein deposits. Brain MRI and nerve/muscle electrical tests will also be performed if not done recently. After this baseline visit, everyone will be followed every 6 months for a total of 2 years (5 visits total). Each follow-up visit includes assessments of thinking, memory, movement, autonomic function, pain, and quality of life, along with a neurological exam and repeat imaging/electrical tests as needed. At the final 24-month visit, another blood sample will be taken for RNA sequencing to see how gene activity changes over time.
This is an observational study; there is no experimental treatment. Participants will be compensated a total of ¥3,000 across all visits for their time and travel. All data and samples will stay in China and will not be shared internationally.
調査の概要
状態
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前：Xian Wang, Principal Investigator
- 電話番号：+86-13269087917
- メール：wangxian_2022@uestc.edu.cn
研究場所
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Sichuan
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Chengdu、Sichuan、中国、610072
- 募集
- Qingyang District
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コンタクト：
- Xian Wang, Principal Investigator
- 電話番号：+86-13269087917
- メール：wangxian_2022@uestc.edu.cn
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参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- Member of a single family (pedigree) with known NOTCH2NLC-related neuronal intranuclear inclusion disease (NIID), including clinically diagnosed patients, asymptomatic GGC repeat expansion carriers, and healthy relatives without the expansion.
- Age 18 to 85 years at the time of enrollment.
- Able and willing to undergo genetic testing for NOTCH2NLC (including long-read sequencing) and a skin punch biopsy.
- Able to provide written informed consent.
Exclusion Criteria:
- Unstable vital signs or any acute medical condition that would interfere with study participation.
- Any condition that, in the opinion of the investigator, makes the participant unsuitable for the study.
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
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NIID Family Cohort
This is a single observational cohort consisting of approximately 12 members of the same family affected by neuronal intranuclear inclusion disease (NIID) caused by GGC repeat expansions in NOTCH2NLC.
The cohort includes individuals with clinically diagnosed NIID, asymptomatic carriers of the repeat expansion, and healthy relatives without the expansion.
After informed consent, all participants will undergo baseline assessments including clinical evaluation, peripheral blood collection for long-read and transcriptome sequencing, a skin punch biopsy for immunohistochemistry, and brain MRI/neurophysiological tests if clinically indicated.
Participants will be followed prospectively every 6 months for 2 years (5 visits total).
Follow-up visits include cognitive, motor, autonomic, and quality-of-life assessments, along with neurological examination and repeat imaging/electrophysiology as needed.
A second blood sample for transcriptome sequencing will be collected at the 24-month visit.
No
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This is an observational study.
No investigational drug, device, biologic, or procedure is administered.
Participants receive only standard clinical assessments, genetic testing, skin biopsy, and regular follow-up evaluations as described in the protocol.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Clinical Severity Score and Its Correlation with NOTCH2NLC GGC Repeat Characteristics
時間枠：Baseline and at Months 6, 12, 18, and 24
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The primary outcome is a composite clinical severity score that integrates cognitive function (assessed by Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]), motor function (including extrapyramidal and pyramidal signs), autonomic function (e.g., orthostatic blood pressure changes, heart rate variability), and peripheral nerve function (based on nerve conduction studies and clinical examination).
Each domain is rated on a standardized scale, and the total score reflects overall neurological impairment, with higher scores indicating greater severity.
The relationship (correlation coefficient) between this score and the NOTCH2NLC GGC repeat number and interruption pattern (defined by long-read sequencing) will be evaluated at baseline and over time.
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Baseline and at Months 6, 12, 18, and 24
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協力者と研究者
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- IRB No. 305 (2026)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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