Penetrance estimation of PRRT2 variants in paroxysmal kinesigenic dyskinesia and infantile convulsions

The objective of this study was to estimate the penetrance ofPRRT2 and determine its influencing factors. We screened 222 PKD index patients and their available relatives, identified 39 families with pathogenic or likely pathogenic (P/LP)PRRT2 variants via Sanger sequencing, and obtained 184 PKD/BFIE/ICCA families with P/LPPRRT2 variants from the literature. Penetrance was estimated as the proportion of affected variant carriers.PRRT2 penetrance estimate was 77.6% (95% confidence interval (CI) 74.5% –80.7%) in relatives and 74.5% (95% CI 70.2%–78.8%) in obligate carriers. In addition, we first observed that penetrance was higher in truncated than in non-truncated variants (75.8% versus 50.0%,P = 0.01), higher in Asian than in Caucasian carriers (81.5% versus 68.5%,P = 0.004), and exhibited no difference in gender or parental transmission. Our results are meaningful for genetic counseling, implying that approximately three-quarters ofPRRT2 variant carriers will developPRRT2-related disorders, with patients from Asia or carrying truncated variants at a higher risk.
Source: Frontiers of Medicine - Category: General Medicine Source Type: research