Recruiting

NCT Number: NCT07670169

Effect of NOTCH2NLC Gene Variations on NIID Clinical Features

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Neuronal Intranuclear Inclusion Disease (NIID) Neuronal intranuclear inclusion disease

Sex eligibility

All sexes

Study type

Observational

Primary location

Qingyang District

Chengdu, Sichuan, 610072, China

Location status: Recruiting

Location contact

Xian Wang, Principal Investigator

CONTACT

[email protected]

+86-13269087917

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

No Intervention: Observational Cohort

Other

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.

Primary outcomes

Clinical Severity Score and Its Correlation with NOTCH2NLC GGC Repeat Characteristics

Time frame: Baseline and at Months 6, 12, 18, and 24

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.

Study contacts

Contact information is provided by the study sponsor or research team.

Xian Wang, Principal Investigator

CONTACT

[email protected]

+86-13269087917

Sponsors and collaborators

Lead sponsor

Sichuan Academy of Medical Sciences