Effect of NOTCH2NLC Gene Variations on NIID Clinical Features (NOTCH2NLC-NIID)
24 de junio de 2026 actualizado por: Sichuan Academy of Medical Sciences
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.
Descripción general del estudio
Estado
Estado
Reclutamiento
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Tipo de estudio
Tipo de estudio
De observación
Inscripción (Estimado)
Inscripción
12
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Estudio Contacto
Estudio Contacto
- Nombre: Xian Wang, Principal Investigator
- Número de teléfono: +86-13269087917
- Correo electrónico: wangxian_2022@uestc.edu.cn
Ubicaciones de estudio
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Sichuan
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Chengdu, Sichuan, Porcelana, 610072
- Reclutamiento
- Qingyang District
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Contacto:
- Xian Wang, Principal Investigator
- Número de teléfono: +86-13269087917
- Correo electrónico: wangxian_2022@uestc.edu.cn
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-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
- Niño
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Sí
Método de muestreo
Muestra no probabilística
Población de estudio
This study will enroll approximately 12 participants from a single family (pedigree) with NOTCH2NLC-related neuronal intranuclear inclusion disease (NIID).
The study population comprises three categories of family members: individuals with a clinical diagnosis of NIID, asymptomatic carriers of the NOTCH2NLC GGC repeat expansion, and healthy relatives who do not carry the expansion.
All participants are adults aged 18 to 85 years recruited from the Health Management Center of Sichuan Provincial People's Hospital in China.
Given the rarity and genetic nature of the disease, this single-family design is intended to control for shared genetic background and environmental factors while examining the effect of different GGC repeat characteristics on clinical phenotype.
Descripción
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.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
Número de grupos/cohortes
1
Cohortes e Intervenciones
Grupo / CohorteGrupo / Cohorte |
Intervención / TratamientoIntervención / Tratamiento |
|---|---|
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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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¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Clinical Severity Score and Its Correlation with NOTCH2NLC GGC Repeat Characteristics
Periodo de tiempo: 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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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Patrocinador
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
Inicio del estudio
1 de abril de 2026
Finalización primaria (Estimado)
Finalización primaria
31 de diciembre de 2028
Finalización del estudio (Estimado)
Finalización del estudio
1 de febrero de 2029
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
1 de junio de 2026
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
24 de junio de 2026
Publicado por primera vez (Actual)
Publicado por primera vez
26 de junio de 2026
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
26 de junio de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
24 de junio de 2026
Última verificación
Última verificación
1 de junio de 2026
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
Otros números de identificación del estudio
- IRB No. 305 (2026)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
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