Digital droplet PCR (ddPCR) to investigate parental mosaicism in New Zealand families with apparently de novo syndromic disorders

Abstract

A recurrence risk of under 1% is usually quoted for parents of children who have apparently de novo genetic conditions. Since 2018, our service has offered digital droplet PCR (ddPCR) testing to determine parental mosaicism rates for apparently de novo variants identified in children with syndromic disorders Aim: To determine the rate of parental mosaicism in a cohort of New Zealand families with apparently de novo pathogenic variants. Method: Specific assays were designed for each pathogenic variant. DNA derived from varying combinations of leukocytes, urothelial buccal and semen was tested by ddPCR for the pathogenic variants identified in the affected children. Results: 102 trio cases have been analysed. Seven parents were identified as being mosaic (6.8%). There is a preponderance of paternal mosaicism (6 of 7 being paternally derived) and two couples had a recurrence of the condition in a second child. Conclusion: This small cohort demonstrates a higher rate of parental mosaicism compared to the typically quoted recurrence risk of <1% and has implications for genetic counselling and genetic testing provision.