Identification and Characterization of Novel Non-Coding Variants That Contribute to Genetic Disorders

Identification and Characterization of Novel Coding, Splicing and Non-Coding Variants That Contribute to Genetic Disorders

The goal of this study is to identify and characterize novel non-coding and splicing variants that may contribute to genetic disorders. We will particularly focus on patients with a diagnosed genetic disorder that has inconclusive genetic findings.

Study Overview

• Status: Suspended
• Conditions: Lysosomal Storage Diseases; Genetic Disease; Inborn Errors of Metabolism; Glycogen Storage Disease; Storage Disease

Detailed Description

To perform this study, we will use patient DNA and RNA that is isolated from blood samples. DNA will be sequenced (targeted capture and/or whole genome DNA sequencing (WGS)) to identify any non-coding single nucleotide variants (SNVs), smaller insertions/deletions (indels), or larger structural variants (SVs). RNA will be sequenced (RNA-seq) to identify genes that are expressed in a differential and/or allele-specific manner, which may indicate a functional non-coding or splicing variant. We will test the function of non-coding variants using high-throughput reporter assays and CRISPR based methodologies.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Erica Nading, MS, CGC; Phone Number: 919-681-2774; Email: erica.nading@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with diagnosed genetic disease and inconclusive genetic results and their unaffected family members

Description

Inclusion criteria:

Subjects will have one or more of the following:

• Patients (probands) diagnosed with a genetic disease
• Patients (probands) with inconclusive genetic results
• Patients (probands) that have identical coding and/or splicing variants, but display highly diverse phenotypes
• Unaffected family members of probands

Exclusion Criteria: There are no exclusion criteria for this study.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of missing pathogenic protein coding variants	2 years

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Priya Kishnani, MD, Duke; Principal Investigator: Greg Crawford, PhD, Duke

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2020
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: May 15, 2020
• First Submitted That Met QC Criteria: May 19, 2020
• First Posted (Actual): May 22, 2020

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 19, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Lysosomal Storage Diseases; Genetic Diseases, Inborn; Glycogen Storage Disease
• Other Study ID Numbers: Pro00090878

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be submitted to dbGaP, casual variants to ClinVar, aggregate rare phenotype and variant data to Geno2MP and other databases, candidate genes via a public list and linked to a node of the MatchMaker Exchange (MyGene2).
• IPD Sharing Time Frame: Data will be available 7-12 months after results are generated and will be available forever.
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No