Genomic Sequencing in Patients With HCM Undergoing Septal Myectomy

NeuroTherapia, Inc.

Status: Completed

Conditions: Gene Product Sequence Variation; Genetic Disease; Hypertrophic Cardiomyopathy

Treatments: Genetic: Genomic sequencing

Study type: Observational

Funder types: Other

Identifiers

NCT03043209

17-090

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 25 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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

Trial design

25 participants in 1 patient group

Genomic sequencing

Description:

Perform Genomic sequencing in peripheral blood DNA and discarded myocardium from cardiac procedures

Treatment:

Genetic: Genomic sequencing