3.3 PDE4DIP Mutations Among Patients with early onset AF and mutation burden analysis
We subsequently screened 7 kindreds with AF and slow ventricular response suggestive of conduction disease using WES. All variants with allele frequencies greater than 1/1,000 or considered as benign by PolyPhen and Sift, including a number of variants in PDE4DIP were filtered. There were 3 independent novel deleterious nonconservative mutations in PDE4DIP gene that segregated with the disease in 4 kindreds (table 1, figure 2 and 3). A mutation burden analysis was then carried out between WES variants of all cases compared to 158 age and ethnically matched controls via Fisher Exact test. Statistical analysis showed significantly higher burden of mutations in PDE4DIP gene in cases vs. controls (adjusted p value <0.05). No other variants AF or heart block genes were identified in the 7 kindreds.