A Natural History Study of hnRNP-related Disorders

Autism Spectrum Disorder Clinical Trial

Official title:

A Natural History Study of hnRNP and Other Gene-related Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03492060
• Other study ID #: AAAR7203
• Status: Recruiting
• Start date: June 13, 2018
• Est. completion date: April 2024

Study information

• Verified date: November 2022
• Source: Columbia University
• Contact: Jennifer M. Bain, MD, PhD
• Phone: 646-426-3876
• Email: jb3634[@]cumc.columbia.edu
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The purpose of this study is to analyze patterns in individuals with hnRNP (and other) genetic variants, including their neurological comorbidities, other medical problems and any treatment. The investigators will maintain an ongoing database of medical data that is otherwise being collected for routine medical care. The investigators will also collect data prospectively in the form of questionnaires, neuropsychological assessments, motor assessments, and electroencephalography to examine the landscape of deleterious variants in these genes.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: April 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Developmental Delay
• Disease
• Hypertonia, Muscle
• Hypotonia
• Intellectual Disability
• Muscle Hypertonia
• Muscle Hypotonia
• Neurodevelopmental Disorders
• Seizures

Locations

Country	Name	City	State
United States	Columbia University Irving Medical Center	New York	New York

Sponsors (5)

Lead Sponsor	Collaborator
Columbia University	Hackensack Meridian Health, New York University, Simons Foundation, Universitätsklinikum Hamburg-Eppendorf

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

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. Det — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Medical abnormalities associated with genetic variants	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.	5 years
Primary	Education-based impairments associated with genetic variants	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.	5 years
Primary	Repetitive Behavior	Correlations (r) between mutant allele (obtained from retrospective data) and repetitive behavior (measured by the Repetitive Behavior Scale - Revised; RBS-R)	5 years
Primary	Sleep Habits	Correlations (r) between mutant allele (obtained from retrospective data) and sleep habits (measured by The Children's Sleep Habits Questionnaire; CSHQ)	5 years
Primary	Sensory Issues	Correlations (r) between mutant allele (obtained from retrospective data) and sensory issues (measured by The Short Sensory Profile; SSP)	5 years
Primary	Social Interaction and Communication SRS-II Score	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)	5 years
Primary	Anxiety	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
Primary	Receptive Language Skills	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)	5 years
Primary	Executive Functioning	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)	5 years
Primary	Autism	Correlations (r) between mutant allele (obtained from retrospective data) and autism (measured by The Childhood Autism Rating Scale; CARS)	5 years
Primary	Adaptive Behavior	Correlations (r) between mutant allele (obtained from retrospective data) and adaptive behavior (measured by The Vineland Adaptive Behavior Scales, Third Edition; Vineland - 3)	5 years
Primary	Social Interaction and Communication SCQ Score	Correlations (r) between mutant allele (obtained from retrospective data) and social interaction and communication issues (measured by The Social Communication Questionnaire; SCQ)	5 years
Primary	Emotional Regulation	Correlations (r) between mutant allele (obtained from retrospective data) and emotional regulation (measured by The Behavioral Assessment System for Children - Third Edition; BASC - 3)	5 years
Primary	Motor Performance	Correlations (r) between mutant allele (obtained from retrospective data) and motor performance (measured by The Movement Assessment Battery for Children - Second Edition; MASC-II)	5 years
Primary	Function in Daily Activities, Mobility, Social and Cognitive, and Responsibility	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)	5 years
Primary	Functional Balance	Correlations (r) between mutant allele (obtained from retrospective data) and functional balance and gross motor function (measured by a 14-item Pediatric Balance Scale)	5 years
Primary	Functional Capability and Mobility	Correlations (r) between mutant allele (obtained from retrospective data) and functional mobility (measured by an 11-point Movement Questionnaire)	5 years
Primary	Coordination and Gait	Correlations (r) between mutant allele (obtained from retrospective data) and gait (measured by a Kinematic Evaluation utilizing Solesound Pedishoe Sandals and GaitRite Walkway)	5 years

External Links

•   Original HNRNPH2 genetic cohort website