PT  - JOURNAL ARTICLE
AU  - Michelle L. Thompson
AU  - Candice R. Finnila
AU  - Kevin M. Bowling
AU  - Kyle B. Brothers
AU  - Matthew B. Neu
AU  - Michelle D. Amaral
AU  - Susan M. Hiatt
AU  - Kelly M. East
AU  - David E. Gray
AU  - James M. J. Lawlor
AU  - Whitley V. Kelley
AU  - Edward J. Lose
AU  - Carla A. Rich
AU  - Shirley Simmons
AU  - Shawn E. Levy
AU  - Richard M. Myers
AU  - Gregory S. Barsh
AU  - E. Martina Bebin
AU  - Gregory M. Cooper
TI  - Genomic sequencing identifies secondary findings in a cohort of parent study participants
AID  - 10.1101/183186
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 183186
4099  - http://biorxiv.org/content/early/2017/12/11/183186.short
4100  - http://biorxiv.org/content/early/2017/12/11/183186.full
AB  - PURPOSE Clinically relevant secondary variants were identified in parents enrolled with a child with developmental delay and intellectual disability.METHODS Exome/genome sequencing and analysis of 789 ‘unaffected’ parents was performed.RESULTS Pathogenic/likely pathogenic variants were identified in 21 genes within 25 individuals (3.2%), with 11 (1.4%) participants harboring variation in a gene defined as clinically actionable by the ACMG. Of the 25 individuals, five carried a variant consistent with a previous clinical diagnosis, thirteen were not previously diagnosed but had symptoms or family history with probable association with the detected variant, and seven reported no symptoms or family history of disease. A limited carrier screen was performed yielding 15 variants in 48 (6.1%) parents. Parents were also analyzed as mate-pairs to identify cases in which both parents were carriers for the same recessive disease; this led to one finding in ATP7B. Four participants had two findings (one carrier and one non-carrier variant). In total, 71 of the 789 enrolled parents (9.0%) received secondary findings.CONCLUSION We provide an overview of the rates and types of clinically relevant secondary findings, which may be useful in the design, and implementation of research and clinical sequencing efforts to identify such findings.