Retrospective diagnosis by parental testing in the next generation sequencing era and utility of reanalysis of exome data

Abstract

AbstractObjectiveGenetic diseases are an important cause of neonatal and childhood mortality. For couples with a history of demise of previous children, screening for carrier status can be done by exome sequencing (ES) of the parents. Our aim was to describe the clinical utility of “targeted parental ES” in such couples and to assess the utility of reanalysis of parental ES data.MethodWe analyzed previous records, including ES reports, of 52 families with demise of previous offspring with a suspected genetic disorder. We also retrieved and reanalyzed raw data of parental ES in FASTQ format from the testing lab.ResultsA potential diagnosis was obtained in 30/52 (57.7%) of couples. We found 38/70 (54.3%) novel variants in this cohort. Shared carrier status for more than one autosomal or X‐linked recessive disorder was identified in 18% of couples. Reanalysis of raw data resulted in a reclassification of variants in 15% of cases.ConclusionTargeted parental ES can be helpful for families with demise of previous offspring with a suspected genetic disorder.