Session Description

This session highlights the 2019 advances made in the genetic etiology of holoprosencephaly using exome sequencing.  We begin with a brief review of the clinical aspects of holoprosencephaly and then work through a case study where exome sequencing resulted in a genetic etiology in a gene not previously associated with human disease.  Next, we describe the results for exome sequencing for a cohort of 322 individuals affected with holoprosencephaly and the translational value of these results.  Finally, we make a case for applying genome sequencing to our cohort, which is currently underway.

Learning Objectives

At the conclusion of the series, participants should be able to:

1. Describe the clinical utility of whole exome/whole genome sequencing tests
2. Identify clinical indications for whole exome/whole genome sequencing
3. List determinants used to assess the probability of a variant’s pathogenicity
4. Elaborate on the importance of pre-test counseling and consent

Session Learning Objectives

At the conclusion of this session, participants should be able to:

1. Describe the clinical characteristics of holoprosencephaly.
2. Identify the four most common genes associated with holoprosencephaly
3. Explain the challenges assigning pathogenicity to variants in new genes associated with holoprosencephaly.
4. Identify the inheritance patterns of holoprosencephaly discussed in this session.

 Faculty:

Paul Kruszka, MD, FACMG

Clinical Geneticist, Associate Research Physician, National Human Genome Research Institute

Donald Hadley, MS, CGC

Associate Director, Office of Clinical Liaison, Associate Investigator, Medical Genetics and Genomic Medicine Training Program, National Human Genome Research Institute

Educational Credits are not offered

Target Audience

1. Clinical geneticists; genetic counselors; pediatric, obstetric, and maternal-fetal specialists; and all medical practitioners who are providing comprehensive diagnostic, management, and counseling services for patients with, or at risk for, genetically influenced health problems.
2. Laboratory directors and technicians who conduct genetic testing, researchers involved in the discovery of genetic disorders and treatments and any healthcare and public health professionals who have an in interest medical and clinical genetics and genomics.

Off-label Drug Use statement

When an off-label use of a product, or an investigational use not yet approved for any purpose, is discussed during an educational activity, the accredited sponsor shall require the speaker to disclose that the product is not labeled for the use under discussion, or that the product is still investigational. Discussions of such uses shall focus on those uses that have been subject of objective investigation.

Disclosures of Financial Relationships

Staff - American College of Medical Genetics and Genomics

The following have nothing to disclose.

Jane Radford, MHA, CHCP

Claudia Barnett

Maximilian Muenke, MD, FACMG

 Presenter Disclosures 

Paul Kruszka, MD, FACMG

Clinical Geneticist, Associate Research Physician, National Human Genome Research Institute

Has no relevant financial relationships to disclose.

Donald Hadley, MS, CGC

Associate Director, Office of Clinical Liaison, Associate Investigator, Medical Genetics and Genomic Medicine Training Program, National Human Genome Research Institute

Has no relevant financial relationships to disclose.