- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03492060
A Natural History Study of hnRNP-related Disorders
A Natural History Study of hnRNP and Other Gene-related Disorders
Study Overview
Status
Detailed Description
Neurodevelopmental disorders are a group of disorders in which the development of the central nervous system is disturbed. The genetic basis for many neurodevelopmental disorders has continued to expand and a recent gene called HNRNPH2 (Heterogeneous Nuclear Ribonucleoprotein H2, encoded by HNRNPH2) is one such gene that is associated with a common neurodevelopmental disorder characterized by developmental delay, intellectual disability, autism and autistic features, and tone abnormalities, among other multisystem problems.
The investigators will expand the genetic cohort to include any individual with a confirmed variant in any gene presenting with neurodevelopmental abnormalities. This is non-interventional study that examines both data previously used in clinical practice and prospective data collection in the form of questionnaires and assessments. The investigators will examine patterns of initial presentation, patterns in neurological evaluations; neurological testing including brain MRI and electroencephalography, and outcomes in individuals with genetic variants.
Genes of Focus:
hnRNPA1 hnRNPA2 hnRNPB1 hnRNPB2 hnRNPC2 hnRNPD hnRNPE1 hnRNPE2 hnRNPE3 hnRNPE4 hnRNPG hnRNPH1 hnRNP H2 hnRNPI hnRNPK hnRNPL hnRNPM hnRNPP hnRNPQ1 hnRNPQ2 hnRNPQ3 hnRNPR hnRNPU
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Jennifer M. Bain, MD, PhD
- Phone Number: 646-426-3876
- Email: jb3634@cumc.columbia.edu
Study Contact Backup
- Name: Joanna Feng
- Email: jlf2218@cumc.columbia.edu
Study Locations
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New York
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New York, New York, United States, 10032
- Recruiting
- Columbia University Irving Medical Center
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Contact:
- Joanna Feng
- Email: jlf2218@cumc.columbia.edu
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Contact:
- Study Team
- Email: hnrnp@columbia.edu
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Sub-Investigator:
- Wendy K. Chung, MD, PhD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Individuals must have had whole genome/exome sequencing and have a confirmed variant in any gene.
Exclusion Criteria:
- Subjects who cannot provide genetic confirmation of a predicted deleterious variant in any gene.
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
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Variant in a hnRNP gene
Individuals with a variant in any hnRNP gene who present with neurodevelopmental abnormalities are eligible for the study.
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Variant in other gene
Individuals with a confirmed variant in other genes who present with neurodevelopmental abnormalities are eligible for the study.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Medical abnormalities associated with genetic variants
Time Frame: 5 years
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Gene variants are known to result in a variety of clinical phenotypes.
The study is intended to accrue data from medical records that document the range of neurological phenotypes and explore their incidence and frequency across genetic cohorts.
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5 years
|
Education-based impairments associated with genetic variants
Time Frame: 5 years
|
The study seeks to collect records from the schools attended by participants; including: Individualized Education Programs (IEPs) and school records.
We intend to use these records, in tandem with medical records, to explore meaningful statistical and clinical relationships in the phenotypes expressed by the population of the study.
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5 years
|
Repetitive Behavior
Time Frame: 5 years
|
Correlations (r) between mutant allele (obtained from retrospective data) and repetitive behavior (measured by the Repetitive Behavior Scale - Revised; RBS-R)
|
5 years
|
Sleep Habits
Time Frame: 5 years
|
Correlations (r) between mutant allele (obtained from retrospective data) and sleep habits (measured by The Children's Sleep Habits Questionnaire; CSHQ)
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5 years
|
Sensory Issues
Time Frame: 5 years
|
Correlations (r) between mutant allele (obtained from retrospective data) and sensory issues (measured by The Short Sensory Profile; SSP)
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5 years
|
Social Interaction and Communication SRS-II Score
Time Frame: 5 years
|
Correlations (r) between mutant allele (obtained from retrospective data) and social interaction and communication issues (measured by The Social Responsiveness Scale - Second Edition; SRS-II)
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5 years
|
Anxiety
Time Frame: 5 years
|
Correlations (r) between mutant allele (obtained from retrospective data) and anxiety (measured by The Spence Children's Anxiety Scale - Preschool and Parent Reports; SCAS - Preschool and SCAS - P)
|
5 years
|
Receptive Language Skills
Time Frame: 5 years
|
Correlations (r) between mutant allele (obtained from retrospective data) and receptive language skills (measured by a 20-item music exposure questionnaire evaluating exposure on a 3-point scale: rarely, sometimes, often; and an EEG with music paradigm)
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5 years
|
Executive Functioning
Time Frame: 5 years
|
Correlations (r) between mutant allele (obtained from retrospective data) and executive functioning (measured by The Behavior Rating Inventory of Executive Function - Parent Report; BRIEF-P)
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5 years
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Autism
Time Frame: 5 years
|
Correlations (r) between mutant allele (obtained from retrospective data) and autism (measured by The Childhood Autism Rating Scale; CARS)
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5 years
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Adaptive Behavior
Time Frame: 5 years
|
Correlations (r) between mutant allele (obtained from retrospective data) and adaptive behavior (measured by The Vineland Adaptive Behavior Scales, Third Edition; Vineland - 3)
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5 years
|
Social Interaction and Communication SCQ Score
Time Frame: 5 years
|
Correlations (r) between mutant allele (obtained from retrospective data) and social interaction and communication issues (measured by The Social Communication Questionnaire; SCQ)
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5 years
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Emotional Regulation
Time Frame: 5 years
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Correlations (r) between mutant allele (obtained from retrospective data) and emotional regulation (measured by The Behavioral Assessment System for Children - Third Edition; BASC - 3)
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5 years
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Motor Performance
Time Frame: 5 years
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Correlations (r) between mutant allele (obtained from retrospective data) and motor performance (measured by The Movement Assessment Battery for Children - Second Edition; MASC-II)
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5 years
|
Function in Daily Activities, Mobility, Social and Cognitive, and Responsibility
Time Frame: 5 years
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Correlations (r) between mutant allele (obtained from retrospective data) and functional capability in daily activities and mobility (measured by The Pediatric Evaluation of Disability Inventory Computer Adaptive Test; PEDI-CAT)
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5 years
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Functional Balance
Time Frame: 5 years
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Correlations (r) between mutant allele (obtained from retrospective data) and functional balance and gross motor function (measured by a 14-item Pediatric Balance Scale)
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5 years
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Functional Capability and Mobility
Time Frame: 5 years
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Correlations (r) between mutant allele (obtained from retrospective data) and functional mobility (measured by an 11-point Movement Questionnaire)
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5 years
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Coordination and Gait
Time Frame: 5 years
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Correlations (r) between mutant allele (obtained from retrospective data) and gait (measured by a Kinematic Evaluation utilizing Solesound Pedishoe Sandals and GaitRite Walkway)
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5 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jennifer M. Bain, MD, PhD, Columbia University
Publications and helpful links
General Publications
- Bain JM, Cho MT, Telegrafi A, Wilson A, Brooks S, Botti C, Gowans G, Autullo LA, Krishnamurthy V, Willing MC, Toler TL, Ben-Zev B, Elpeleg O, Shen Y, Retterer K, Monaghan KG, Chung WK. Variants in HNRNPH2 on the X Chromosome Are Associated with a Neurodevelopmental Disorder in Females. Am J Hum Genet. 2016 Sep 1;99(3):728-734. doi: 10.1016/j.ajhg.2016.06.028. Epub 2016 Aug 18.
- Bain JM, Thornburg O, Pan C, Rome-Martin D, Boyle L, Fan X, Devinsky O, Frye R, Hamp S, Keator CG, LaMarca NM, Maddocks ABR, Madruga-Garrido M, Niederhoffer KY, Novara F, Peron A, Poole-Di Salvo E, Salazar R, Skinner SA, Soares G, Goldman S, Chung WK. Detailed Clinical and Psychological Phenotype of the X-linked HNRNPH2-Related Neurodevelopmental Disorder. Neurol Genet. 2021 Jan 29;7(1):e551. doi: 10.1212/NXG.0000000000000551. eCollection 2021 Feb.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Pathologic Processes
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Neuromuscular Manifestations
- Child Development Disorders, Pervasive
- Disease
- Seizures
- Autism Spectrum Disorder
- Muscle Hypertonia
- Intellectual Disability
- Neurodevelopmental Disorders
- Muscle Hypotonia
Other Study ID Numbers
- AAAR7203
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
- Clinical Study Report (CSR)
- Analytic Code
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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