Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jun;60(6):e63-e66.
doi: 10.1111/epi.15187. Epub 2019 May 11.

Parental mosaicism in epilepsies due to alleged de novo variants

Rikke S Møller  1   2 , Nora Liebmann  3 , Line H G Larsen  4 , Mathias Stiller  3 , Julia Hentschel  3 , Nahrain Kako  4 , Dalia Abdin  5 , Nataliya Di Donato  5 , Deb K Pal  6   7   8   9 , Pia Zacher  10 , Steffen Syrbe  11 , Hans A Dahl  4 , Johannes R Lemke  3
Affiliations

Parental mosaicism in epilepsies due to alleged de novo variants

Rikke S Møller et al. Epilepsia. 2019 Jun.

Abstract

Severe early onset epilepsies are often caused by de novo pathogenic variants. Few studies have reported the frequency of somatic mosaicism in parents of children with severe epileptic encephalopathies. Here we aim to investigate the frequency of mosaicism in the parents of children with epilepsy caused by alleged de novo variants. We tested parental genomic DNA derived from different tissues for 75 cases using targeted next-generation sequencing. Five parents (6.6%) showed mosaicism at minor allele frequencies of 0.8%-29% for the pathogenic variant detected in their offspring. Parental mosaicism was observed in the following genes: SCN1A, SCN2A, SCN8A, and STXBP1. One of the identified parents had epilepsy himself. Our results show that de novo events can occur already in parental tissue and in some cases can be detected in peripheral blood. Consequently, parents affected by low-grade mosaicism are faced with an increased recurrence risk for transmitting the pathogenic variant, compared to the overall recurrence risk for a second affected child estimated at approximately 1%. However, testing for parental somatic mosaicism will help identifying those parents who truly are at higher risk and will significantly improve genetic counseling in the respective families.

Keywords: de novo variants; epileptic encephalopathies; next-generation sequencing; parental mosaicism; recurrence risk.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types