Mosaic mutations in early-onset genetic diseases

Matt Halvorsen, Slavé Petrovski, Renée Shellhaas, Yingying Tang, Laura Crandall, David Goldstein, Orrin Devinsky

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Purpose:An emerging approach in medical genetics is to identify de novo mutations in patients with severe early-onset genetic disease that are absent in population controls and in the patient's parents. This approach, however, frequently misses post-zygotic "mosaic" mutations that are present in only a portion of the healthy parents' cells and are transmitted to offspring.Methods:We constructed a mosaic transmission screen for variants that have an ∼50% alternative allele ratio in the proband but are significantly less than 50% in the transmitting parent. We applied it to two family-based genetic disease cohorts consisting of 9 cases of sudden unexplained death in childhood (SUDC) and 338 previously published cases of epileptic encephalopathy.Results:The screen identified six parental-mosaic transmissions across the two cohorts. The resultant rate of ∼0.02 identified transmissions per trio is far lower than that of de novo mutations. Among these transmissions were two likely disease-causing mutations: an SCN1A mutation transmitted to an SUDC proband and her sibling with Dravet syndrome, as well as an SLC6A1 mutation in a proband with epileptic encephalopathy.Conclusion:These results highlight explicit screening for mosaic mutations as an important complement to the established approach of screening for de novo mutations.

Original languageEnglish
Pages (from-to)746-749
Number of pages4
JournalGenetics in Medicine
Issue number7
StatePublished - Jul 1 2016


  • epilepsy; mosaic; mutation; sudden unexplained death in childhood; whole-exome sequencing


Dive into the research topics of 'Mosaic mutations in early-onset genetic diseases'. Together they form a unique fingerprint.

Cite this