Genomic case conferences are on-demand webinars that focus on the adaptation of exome or genome sequencing technology in clinical care. During the ACMG Genomics Case Conferences, expert(s) from select institutions will present and lead discussions on an intriguing, complex and/or difficult patient cases in the area of genomics. Genomic Case Conferences are free for Members/Trainees (credits not included).

Session Description:
For many decades chromosome studies were the gold standard of cytogenetic testing for patients with abnormal congenital phenotypes. Chromosomal microarray (CMA) has replaced karyotype as a first-tier test for these patients; however, chromosome studies are still utilized to some degree, particularly following a normal microarray study. Chromosome studies have the ability to detect apparently balanced rearrangements such as translocation, but without a molecular understanding of the breakpoints of the rearrangement in question, those findings most often have uncertain clinical significance. Similarly, CMA studies frequently detect copy number gains with breakpoint boundaries that may or may not disrupt genes associated with an abnormal phenotype resulting from haploinsufficiency. Parental testing to distinguish inherited from de novo events is recommended in these scenarios; however, patients are still frequently left with results of uncertain clinical significance. Mate pair sequencing (MPseq) has been shown to be a useful strategy to characterize such rearrangements, providing clarity to the significance of such rearrangements in many cases. This session will explain how MPseq works, describe situations in which this assay is useful, and summarize the clinical experience of this assay to date with respect to sensitivity and success rate with respect to re-classifying variants of uncertain significance.

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. Discuss the current gaps that exist in clinical cytogenetic testing
2. Describe how mate pair sequencing works and how it differs from other forms of whole genome sequencing
3. Identify situations in which mate pair sequencing can be used to aid in the interpretation of results of uncertain clinical significance

 FINANCIAL DISCLOSURES

Planning Committee

Monica Giovanni, MS, CGC

ACMG Education Committee Chair and Liaison to the Program Committee

Nothing to disclose

 

Anne Slavotinek, MB.BS., PhD, FACMG

University of California, San Francisco (UCSF)

Disclosures: Grant/Research Support National Eye Institute and National Institutes of Health; Royalties: Oxford University Press, UptoDate

 

John Bernat, MD, PhD, FACMG

University of Iowa

Disclosures: Receives grant/research support from Sanofi Genzyme, Shire and Protalix

 

Staff - American College of Medical Genetics and Genomics

The following have nothing to disclose.

Jane Radford, MHA, CHCP

Claudia Barnett

Michael Watson, PhD, FACMG

 

Presenter Disclosures

Nicole Hoppman, PhD, FACMG

Co-Director, Genomics Laboratory,

Mayo Clinic

Nothing to disclose

 

Elyse Mitchell, MS, LCGC

Genetic Counselor, Genomics Laboratory,

Mayo Clinic

Nothing to disclose