ESHG19: calculating recurrence risk of de novo mutation disorders


  • Dawn O'Shea
  • Univadis Medical News
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Researchers have developed a strategy to calculate the risk of recurrence of congenital conditions for parents of a child affected by a disorder caused by a de novo mutation (DNMs).

The Precision Genetic Counselling and Reproduction (PREGCARE) study aimed to develop a systematic strategy to identify high-risk mosaic (present in multiple parental gonadal cells) DNMs and provide families with a personalised assessment of transmission risk.

At the European Society of Human Genetics annual conference in Sweden last weekend, the study authors presented data from 20 families. Individual risk stratification was achieved through analysis of 14 tissue samples of various embryonic origin from the family trio (mother, father, offspring).

While instances of mosaicism, such as a maternally originating KIF11 mutation, were detected for most families, the DNM was undetectable by deep sequencing of parental samples. Long-read haplotyping confirmed that these families had an extremely low risk (≤0.1%) of having another affected child.

While disorders caused by DNMs are usually assumed to be one-off events, in practice, the same mutation recurs in a subsequent pregnancy in 1-2 per cent of cases. The authors said this strategy should reassure close to 75 per cent of parents of an affected child that their recurrence risk is negligible.