Robust identification of mosaic variants in congenital heart disease

Kathryn B. Manheimer, Felix Richter, Lisa J. Edelmann, Sunita L. D’Souza, Lisong Shi, Yufeng Shen, Jason Homsy, Marko T. Boskovski, Angela C. Tai, Joshua Gorham, Christopher Yasso, Elizabeth Goldmuntz, Martina Brueckner, Richard P. Lifton, Wendy K. Chung, Christine E. Seidman, J. G. Seidman, Bruce D. Gelb

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Mosaicism due to somatic mutations can cause multiple diseases including cancer, developmental and overgrowth syndromes, neurodevelopmental disorders, autoinflammatory diseases, and atrial fibrillation. With the increased use of next generation sequencing technology, multiple tools have been developed to identify low-frequency variants, specifically from matched tumor-normal tissues in cancer studies. To investigate whether mosaic variants are implicated in congenital heart disease (CHD), we developed a pipeline using the cancer somatic variant caller MuTect to identify mosaic variants in whole-exome sequencing (WES) data from a cohort of parent/affected child trios (n = 715) and a cohort of healthy individuals (n = 416). This is a novel application of the somatic variant caller designed for cancer to WES trio data. We identified two cases with mosaic KMT2D mutations that are likely pathogenic for CHD, but conclude that, overall, mosaicism detectable in peripheral blood or saliva does not account for a significant portion of CHD etiology.

Original languageEnglish
Pages (from-to)183-193
Number of pages11
JournalHuman Genetics
Issue number2
StatePublished - 1 Feb 2018


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