Table 3

Components of genetic counselling for a DNM discovered in a child

FactorImpact on recurrence risk
Parental gonadal mosaicismDepending on the type and VAF of the mutation. Mosaicisms in mothers double the probability of recurrence, but the probability is increased more than 50 times in fathers11
DNMs shared by siblingsIncreases to 23.0% from 1.1%14
Mutation originApproximately 80% of all DNMs arise in the paternal allele, but mutations of maternal origin determine a higher recurrence risk than paternal mutations11 46
Age of motherUnlikely to change with maternal age11
Age of fatherDespite an increased risk of a first afflicted offspring, the recurrence risk from paternal mutations diminishes with age11
  • DNM, de novo mutation.