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. There are four overall learning objectives that will be covered in each session.

Session Description:
“Women have two X chromosomes, but men have an X and a Y.” The X chromosome has a critical role in genetics, but is often less considered than the autosomes. This session will use whole exome sequencing (WES) results to review the biology of the X-chromosome, including X-linked patterns of inheritance and X-inactivation. Presenters will provide examples of WES results that describe sequence variants in newly identified genes causing X-linked ID. They will also discuss the merits of WES versus panel testing for individuals with X-linked ID and for individuals with ID that has an unknown inheritance pattern.

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 the session, participants should be able to:

1. Explain the principles of X-linked recessive and X-linked dominant inheritance
2. Describe the mechanism for X-inactivation and how this can influence clinical findings
3. Discuss the contribution of X-linked genes to intellectual disability and to be aware of recently identified X-linked genes
4. Explain the advantages and disadvantages of whole exome sequencing versus panel testing for X-linked intellectual disability, and also for testing for intellectual disability in which the inheritance pattern is not known

 

 FINANCIAL DISCLOSURES

 

Planning Committee

Monica Giovanni, MS, CGC

Geisinger Health System, Brookline, MA

Nothing to disclose

 

Liming Bao, MD, PhD, FACMG

Dartmouth-Hitchchcock Medical Center

Nothing to disclose

 

Christian Schaaf, MD, PhD, FACMG

Baylor College of Medicine and Jan & Dan Duncan Neurological Research Institute, Houston, TX

Nothing to disclose

 

Staff - American College of Medical Genetics and Genomics

Jane Radford, MHA, CHCP

Nothing to disclose

 

Michael Watson, PhD, FACMG

Nothing to disclose

 

Faculty – University of California, San Francisco

Jude Abadie, PhD

Molecular Genetics Fellow

Nothing to disclose

 

Marta Sabbadini, PhD, MS, LCGC

Genetic Counselor, Biochemical Genetics and Personalized Genomics

Nothing to disclose

 

Anne Slavotinek, MBBS, PhD, FACMG

Professor of Clinical Pediatrics

Royalties Up to date; Oxford University Press

 

Jessica Van Ziffle, PhD

Assistant Professor of Pathology

Nothing to disclose