Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation.

ABSTRACT: Following the diagnosis of a paediatric disorder caused by an apparently de novo mutation, a recurrence risk of 1-2% is frequently quoted due to the possibility of parental germline mosaicism; but for any specific couple, this figure is usually incorrect. We present a systematic approach to providing individualized recurrence risk. By combining locus-specific sequencing of multiple tissues to detect occult mosaicism with long-read sequencing to determine the parent-of-origin of the mutation, we show that we can stratify the majority of couples into one of seven discrete categories associated with substantially different risks to future offspring. Among 58 families with a single affected offspring (representing 59 de novo mutations in 49 genes), the recurrence risk for 35 (59%) was decrease

SUBMITTER: Bernkopf M 

PROVIDER: S-EPMC9932158 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature