Genetic Disease, Glycogen Storage Disease, Inborn Errors of Metabolism, Lysosomal Storage Diseases, Storage Disease
Conditions
Brief summary
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.
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.
Interventions
None listed
Sponsors
Duke University
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of missing pathogenic protein coding variants | 2 years |
Countries
United States
Outcome results
None listed