Experts dispute 9 of 17 genes once linked to long QT syndrome
A panel of experts from the Clinical Genome Resource (ClinGen) are publicly disputing nine of 17 genes once thought to be linked to long QT syndrome.
In their report, published in Circulation Jan. 27, senior author Michael Gollob, MD, of the Toronto General Hospital Research Institute, and colleagues detailed a “genetic research race” that’s been underway since 1957, when researchers first identified long QT syndrome as a cardiac condition. They said that to date experts have compiled 17 genes they believe are linked to the illness, which is caused by mutations in genes that regulate electrical CV activity.
Arrhythmias provoked by long QT syndrome can have a direct cause—exercise, for example, or high stress—or they can be completely random, but there’s always a chance they can be fatal. Gollob et al. said most people with the condition don’t know they have it unless they undergo an ECG and genetic testing and know their family history.
ClinGen is funded by the National Human Genome Research Institute (NHGRI), which is itself part of the National Institutes of Health. Erin Ramos, PhD, a project scientist for ClinGen and program director for the division of genomic medicine at NHGRI, said in a release that NHGRI developed ClinGen as a way to standardize guidelines for genetic testing. A panel of experts, including researchers, clinicians and genetic counselors comb through scientific evidence from research papers to identify gene-disease relationships as either “definitive,” “strong,” “moderate,” “limited,” “disputed” or “refuted.”
The experts reported that three genes—KCNQ1, KCNH2 and SCN5A—were indeed backed by enough evidence to be categorized as “definitive” genetic triggers for long QT syndrome. They classified four other genes as either “strong” or “definitive” for causing atypical forms of long QT syndrome, but the panel didn’t find enough evidence to support the remaining 10 genes.
Those 10 genes were all placed in either the “limited” or “disputed” category for their link to long QT syndrome, and for that reason the authors said they don’t recommend using them as markers in routine clinical tests.
“Our study highlights the need to take a step back and to critically evaluate the level of evidence for all reported gene-disease associations, especially when applying genetic testing for diagnostic purposes in our patients,” Gollob said in a statement. “Testing genes with insufficient evidence to support disease causation only creates a risk of inappropriately interpreting the genetic information and leading to patient harm.”
After graduating from Indiana University-Bloomington with a bachelor’s in journalism, Anicka joined TriMed’s Chicago team in 2017 covering cardiology. Close to her heart is long-form journalism, Pilot G-2 pens, dark chocolate and her dog Harper Lee.