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Effect of NOTCH2NLC Gene Variations on NIID Clinical Features (NOTCH2NLC-NIID)

24. juni 2026 oppdatert av: 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.

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Studietype

Observasjonsmessig

Registrering (Antatt)

12

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studiesteder

  • Kina
    • Sichuan
      • Chengdu, Sichuan, Kina, 610072
        • Rekruttering
        • Qingyang District
        • Ta kontakt med:

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Barn
  • Voksen
  • Eldre voksen

Tar imot friske frivillige

Ja

Prøvetakingsmetode

Ikke-sannsynlighetsprøve

Studiepopulasjon

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.

Beskrivelse

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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

Kohorter og intervensjoner

Gruppe / Kohort
Intervensjon / Behandling
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
Annen: No Intervention: Observational Cohort
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.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Clinical Severity Score and Its Correlation with NOTCH2NLC GGC Repeat Characteristics
Tidsramme: 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.
Baseline and at Months 6, 12, 18, and 24

Samarbeidspartnere og etterforskere

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Sponsor

Sichuan Academy of Medical Sciences

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

1. april 2026

Primær fullføring (Antatt)

31. desember 2028

Studiet fullført (Antatt)

1. februar 2029

Datoer for studieregistrering

Først innsendt

1. juni 2026

Først innsendt som oppfylte QC-kriteriene

24. juni 2026

Først lagt ut (Faktiske)

26. juni 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

26. juni 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

24. juni 2026

Sist bekreftet

1. juni 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • IRB No. 305 (2026)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

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