The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care

Kaul, Karen L.; Sabatini, Linda M.; Tsongalis, Gregory J.; Caliendo, Angela M.; Olsen, Randall J.; Ashwood, Edward R.; Bale, Sherri; Benirschke, Robert; Carlow, Dean; Funke, Birgit H.; Grody, Wayne W.; Hayden, Randall T.; Hegde, Madhuri; Lyon, Elaine; Murata, Kazunori; Pessin, Melissa; Press, Richard D.; Thomson, Richard B.

Whole-exome sequencing (WES) involves evaluating the coding regions of all *20 000 human genes at once, to search for the underlying molecular cause of an undiagnosed but presumed genetic disorder. These tests are used for patients who already have undergone extensive genetic diagnostic testing and exhausted the (limited) FDA and LDP singlegene tests or in cases where it is more cost-and timeeffective to start with WES. Whole-exome sequencing is used for the so-called "diagnostic odyssey" patient and has a high diagnostic yield for these patients, with 25% to 30% of studies yielding a diagnosis. 134, 135 The tests are highly complex and involve capture of the relevant DNA segments, sequencing of those segments, bioinformatics approaches to sequence alignment and identification of variants (differences between patient DNA and reference), interpretation of the identified variants, and report generation. Under CLIA and NYSDOH, the technical validation data collected by the laboratory prior to offering WES are required, and the laboratory participates in ongoing PT (through CAP and sample exchanges) to demonstrate assay quality.