During The ACMG Genomics Case Conferences, a team from select institutions will present and lead discussions on an intriguing, complex and/or difficult patient case in the area of genomics. The primary focus of these case conferences will be on the adaptation of exome or genome sequencing technology in clinical care.

Session Description:
Somatic variation is well recognized in relation to tumor mutation profiling in cancer genetics. More recently, somatic variation has been discovered as the underlying cause for a number of congenital disorders with overgrowth as one of the primary clinical phenotypes. In addition to overgrowth, many of these disorders harbor additional overlapping clinical features including but not limited to skin lesions, vascular anomalies and various neurological findings. To date, the vast majority of mutations detected in affected individuals have been found in the PI3K/AKT/mTOR pathway. Due to the mosaic nature of this group of syndromes, testing requires deep sequencing of an affected tissue sample to uncover low variant allele fraction alterations responsible for disease. Genomics and Pathology Services at Washington University in St. Louis developed testing for somatic overgrowth and related disorders using a target hybrid capture based next-generation sequencing assay. This webinar will review overgrowth related disorders and our current clinical assay including a summary of our lab cohort to date and highlighted case studies.

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. Illustrate the utility of next-generation sequencing in the detection of low variant allelic frequency somatic alterations
2. Review the genes interrogated on the testing panels and understand the relevance of these genes to the phenotype of the patient
3. Establish that the somatic etiology of overgrowth disorders necessitates genetic evaluation of involved tissue rather than blood
4. Demonstrate the frequency of genetic variation associated with somatic overgrowth disorders in a clinical laboratory cohort

 

 FINANCIAL DISCLOSURES

Planning Committee

Monica Giovanni, MS, CGC

Geisinger Health System, Brookline, MA

Nothing to disclose

 

Liming Bao, MD, PhD, FACMG

Dartmouth-Hitchcock Medical Center

Nothing to disclose

 

Staff - American College of Medical Genetics and Genomics

The following have nothing to disclose.

Jane Radford, MHA, CHCP

Claudia Barnett

Michael Watson, PhD, FACMG

 

Contributors: Washington University School of Medicine

The following have nothing to disclose.

Julie Ann Neidich, MD, FACMG, FAAP

Associate Professor and Medical Director, Cytogenomics & Molecular Pathology Laboratory

Washington University School of Medicine

 

Presenters and Disclosures

The following have nothing to disclose.

 

Meagan Corliss, MS, CGC; Genetic Counselor

Washington University School of Medicine

Latisha Love-Gregory, PhD; Project Coordinator
Washington University School of Medicine