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.