Clinical Significance of Ryanodine Receptor-1 (RYR-1) Gene Variants:

New Insights into Pathophysiology, Diagnosis, and Treatment of RYR1-Linked Diseases

Chestnut Residence & Conference Centre (University of Toronto) @ 89 Chestnut Street

November 1, 2013 - Day 1 (Colony Centre & West 2^nd Floor)

7:00 – 7:45 Continental Breakfast (Colony Centre Foyer)

7:45 - 8:00 Henry Rosenberg, Saint Barnabas Health

Welcome and Meeting Overview

Session I: RYR1 Physiology and Pathophysiology

8:00 – 10:00 Robert T. Dirksen, University of Rochester

Session Chair

All presentations 25 min plus 5 min for discussion

8:00 – 8:30 Filip Van Petegem, University of British Columbia

High Resolution Structures of RyR1 Domains

8:30 – 9:00 Clara Franzini-Armstrong, University of Pennsylvania

Impact of EC coupling Proteins on Triad Structure

9:00 – 9:30 Susan L. Hamilton, Baylor College of Medicine

Modulation of RYR1 Function: Environmental and Pharmacological

9:30 – 10:00 James J. Dowling, Hospital for Sick Children and University of Toronto

RYR1 Related Myopathies: Genotype-Phenotype Correlations and New Treatment Perspectives

10:00 - 10:30 Coffee Break (Colony Centre Foyer)

Session II: RYR1-Associated Disorders and Treatment

10:30 – 12:30 Robert T. Dirksen, University of Rochester

Session Chair

10:30 - 11:00 Jerome Parness, University of Pittsburgh

Dantrolene Mechanism of Action: Uses in MH and Other Disorders

(25 min talk + 5 min Discussion)

11:00 – 11:30 Georgirene D. Vladutiu, University at Buffalo

RyR1, CACNA1S and Statin Myopathies

(25 min talk + 5 min Discussion)

11:30 - 11:50 Francis O’Connor, Uniformed Services University of Health Sciences

Heat/exercise-induced Rhabdomyolysis and MH: Clinical Perspectives

11:50 - 12:10 John Capacchione, Uniformed Services University of Health Sciences

Heat/exercise-induced Rhabdomyolysis and MH: Genetic Perspectives

12:10 – 12:30 Discussion of Heat/exercise-induced Rhabdomyolysis and MH

12:30 - 2:30 Lunch (Colony Centre Foyer) and Poster Session (Colony Centre & West)

Session III: Diagnosis of MH Susceptibility: Current and Future

2:30 – 4:15 Philip Hopkins, University of Leeds

Session Chair

2:30 – 3:00 Sheila M. Muldoon, Uniformed Services University of Health Sciences

Contracture Testing: Updates and Standardization

3:00 - 3:30 Khishge Sambuughin, Uniformed Services University of Health Sciences

MH Genetic Testing in the Genomic Era

3:30 - 4:00 Philip Hopkins, University of Leeds

MH Genetic Screening: RYR1 Variants, Exome Sequencing, New Genes

4:00 - 4:15 Philip Hopkins, University of Leeds

Summary and Open Discussion

4:15 - 4:45 Coffee Break (Colony Centre Foyer)

Session IV: Practical Clinical Cases

4:45 – 5:45 Barbara Brandom, University of Pittsburgh

Session Chair

4:45 - 5:15 Marilyn G. Larach, MHAUS

Failure to Rescue from Fulminant Malignant Hyperthermia: Deaths &

their Genetic Variants, 2007-2012

5:15 - 5:45 Phenotype and Genotype: Case Presentations

John Capacchione, Uniformed Services University of Health Sciences

Sheila Riazi, University of Toronto

Henry Rosenberg, Barnabas Health

Philip Hopkins, University of Leeds

6:45 - 7:45 Dinner at Chestnut Residence & Conference Center

In Colony Centre & West 2^nd Floor

7:45 – 8:45 Keynote Lecture

Dr. Wayne Chen, University of Calgary

"Mechanisms and Treatment of RYR-associated Diseases”

Clinical Significance of Ryanodine Receptor-1 (RYR-1) Gene Variants:

New Insights into Pathophysiology, Diagnosis, and Treatment of RYR1-Linked Diseases

November 2, 2013 - Day 2 (Colony Centre & West 2^nd Floor)

Session V: Evaluating Risk in Patients with RYR1 Variants

7:00 – 8:00 Continental Breakfast (Colony Centre Foyer)

8:00 – 10:00 Henry Rosenberg, Saint Barnabas Health

Session Chair

8:00 - 8:45 James Weber, PreventionGenetics

Commercial Laboratory Experiences with Genetic Testing of MH

8:45 - 9:30 Panel-led Discussion: "Problems of Variants of Unknown Significance”

James J. Dowling, Hospital for Sick Children and University of Toronto

Philip Hopkins, University of Leeds

Khishge Sambuughin, Uniformed Services University of Health Sciences

Deanna Steele, University of Pittsburgh

9:30 - 10:00 Mark Tarnopolsky, McMaster University

Evaluation and Guidance of Patients with Myopathy

10:00 - 10:30 Coffee Break (Colony Centre Foyer)

Session VI: Databases and How They Influence Clinical Care

10:30 – 12:30 Henry Rosenberg, Saint Barnabas Health

Session Chair

10:30 - 11:00 Donna Maglott, National Center of Biological Information

Role of Genetic Databases in Risk Assessment and Resources for Scientists, Clinicians, Genetic Counselors, and Patients

11:00 - 11:30 Barbara Brandom, University of Pittsburgh

Contributions of NAMHR to the Global Rare Disease Registry

11:30 - 12:00 Henry Rosenberg, Saint Barnabas Health

Role of MHAUS in Gathering Data, Dissemination and Education

12:00 - 12:30 Conference Summary and Future Directions

Robert T. Dirksen, University of Rochester

Sheila M. Muldoon, Uniformed Services University of Health Sciences

Sheila Riazi, University of Toronto

Henry Rosenberg, Saint Barnabas Health