A Garvan Institute of Medical Research- and University of New South Wales Sydney-led team reporting in Genome Medicine explores genomic contributions to inherited cardiac disease diagnoses and management at a multidisciplinary clinic at Sydney's Royal Prince Alfred Hospital that specializes in dealing with inherited cardiomyopathies and other heart conditions. Across almost 1,700 cases considered consecutively from 2002 to 2020, the researchers focused on 888 individuals who met the study's inclusion criteria, including the availability of genetic testing and clinical profiles. Of those cases, genetic testing uncovered pathogenic or likely pathogenic variants in 37 percent of cases and variants of uncertain significance (VUS) in another 8 percent, they report, with genetic results impacting diagnoses or care for 51 individuals. The authors note that diagnostic yields were highest for cases suspected of stemming from monogenic disease based on a score that encompassed family history, age of disease onset, and disease severity, while VUS rates ranged from some 10 percent in individuals of European ancestry to 15 percent or 20 percent in individuals from other ancestry groups. "We describe the role of genomics in elucidating an overall diagnosis and propose a simple scoring system for prioritizing difficult unsolved cases most likely to have a monogenic disease basis," the authors write. "Clarifying the underlying diagnosis in these unsolved cases may provide important insights about disease mechanisms and lead to an increased yield of cardiac genetic testing with the potential for important clinical and prognostic implications worldwide."
Inherited Cardiac Disease Genetic Diagnoses Linked to Ancestry, Monogenic Disease Score
Jan 03, 2023