Genomic Sequencing in Patients With HCM Undergoing Septal Myectomy

Study Overview
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Brief Summary
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Investigators aim to use comparative exome and/or genome sequencing to discover causative molecular lesions for phenotypes hypothesized to be caused by somatic mutations. For this study, investigators have targeted hypertrophic cardiomyopathy.

Detailed Description
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The hypothesis is that sporadic or simplex occurrences of what are typically autosomal dominantly inherited diseases can instead be caused my mosaic mutations, specifically, mutations in the heart itself. This hypothesis mandates that investigators sequence both affected and unaffected tissues, which in this case, investigators will construe to be peripheral blood DNA and discarded myocardium from cardiac procedures. Eligible individuals will first undergo informed consent to be part of the study prior to their scheduled myomectomy. The study participants will also have phlebotomy for research samples. The NIH Intramural Sequencing Center (NISC) will perform paired exome or genome sequencing and we will first screen for germline mutations in known cardiomyopathy genes that meet ACMG standards of likely pathogenic or pathogenic. Then, if this is negative, investigators will screen for sequence variants that are present in cardiac tissue but absent in the blood DNA. Investigators will also screen blood DNA for secondary findings in genes recommended for annotation and results return by the ACMG and sequence variants deemed clinically relevant in this gene set will be validated in a CLIA-certified laboratory and the results returned to that participant.

Official Title
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Genomic Sequencing in Patients With Hypertrophic Cardiomyopathy Undergoing Septal Myectomy

Conditions
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Hypertrophic Cardiomyopathy, Genetic Disease, Gene Product Sequence Variation

Intervention / Treatment
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* Genetic: Genomic sequencing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is 18 years and older has a clinical diagnosis of hypertrophic cardiomyopathy. Patient scheduled for clinically-indicated myomectomy. Patient has a negative family history of hypertrophic cardiomyopathy Patient is willing to receive results of secondary variant screen Exclusion Criteria: Pregnant Inability to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Genomic sequencing<br>Perform Genomic sequencing in peripheral blood DNA and discarded myocardium from cardiac procedures | Genetic: Genomic sequencing<br>* Genomic sequencing of DNA in Blood sample and myectomy tissue<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genetic causes of HCM in patients without a strong family history of the condition | The investigators will use DNA testing technology called genomic sequencing | one year |