Genomic Diagnostics Within a Medically Underserved Population: Efficacy and Implications
© American College of Medical Genetics and Genomics ORIGINAL RESEARCH ARTICLE Genomic diagnostics within a medically underserved population: efficacy and implications Kevin A. Strauss, MD1, Claudia Gonzaga-Jauregui, PhD2, Karlla W. Brigatti, MS1, Katie B. Williams, MD, PhD1, Alejandra K. King, PhD2, Cristopher Van Hout, PhD2, Donna L. Robinson, CRNP1, Millie Young, RNC1, Kavita Praveen, PhD2, Adam D. Heaps, MS1, Mindy Kuebler, MS1, Aris Baras, MD2, Jeffrey G. Reid, PhD2, John D. Overton, PhD2, Frederick E. Dewey, MD2, Robert N. Jinks, PhD3, Ian Finnegan, BA3, Scott J. Mellis, MD, PhD2, Alan R. Shuldiner, MD2 and Erik G. Puffenberger, PhD1 Purpose: We integrated whole-exome sequencing (WES) and Compared to trio analysis, “family” WES (average seven exomes chromosomal microarray analysis (CMA) into a clinical workflow per proband) reduced filtered candidate variants from 22 ± 6to to serve an endogamous, uninsured, agrarian community. 5 ± 3 per proband. Nineteen (51%) alleles were de novo and 17 Methods: Seventy-nine probands (newborn to 49.8 years) who (46%) inherited; the latter added to a population-based diagnostic presented between 1998 and 2015 remained undiagnosed after panel. We found actionable secondary variants in 21 (4.2%) of 502 biochemical and molecular investigations. We generated WES data subjects, all of whom opted to be informed. for probands and family members and vetted variants through Conclusion: CMA and family-based WES streamline and rephenotyping, segregation analyses, and population studies. economize diagnosis of rare genetic disorders, accelerate novel Results: The most common presentation was neurological disease gene discovery, and create new opportunities for community-based (64%). Seven (9%) probands were diagnosed by CMA.
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