The diagnostic landscape for rare disease is being reshaped by whole exome sequencing, which is increasingly used as a first-line test for cases involving unexplained developmental delay, epilepsy, or multisystem disease. In this episode, Rebecca Johnson Wheeler, MS, CGC, explores how whole exome sequencing and Quest Diagnostics genetic experts are transforming rare disease diagnosis by enabling earlier answers, reducing unnecessary testing, and improving care for patients and families. This episode will Describe whole exome sequencing in rare disease (1:40) Review clinical indications and guidelines for whole exome sequencing, including the available test options (3:25) Explain the role of genetic counselors in supporting rare disease and whole exome sequencing (5:50) Date: May 2026 Speaker(s): Rebecca Johnson Wheeler, MS, CGC Contributor(s): Rebecca Johnson Wheeler, MS, CGC; Maeson Latsko, PhD; Meenakshi Mahey Kumar, MS, CGC; Natalie Cuttic; Whitney Dodge, MS, CGC; Khalida Liaquat, MS, CGC Additional resources: Quest Diagnostics Clinical Education Center [Link] Test information: https://www.questdiagnostics.com/healthcare-professionals/about-our-tests/genetics/exome Blog: https://www.questdiagnostics.com/our-company/actions-insights/2026-blogs/considering-mitochondrial-genomes-in-whole-exome-testing Ordering information: Whole Exome | Test Detail | Quest Diagnostics Whole Exome Family Trio | Test Detail | Quest Diagnostics Whole Exome Family Duo | Test Detail | Quest Diagnostics References: Reinholdt L, Chesler E, Pera M, Rosenthal N. The rare-to-common disease journey: a winding road to new therapies. Trends Genet. 2025;41(9):762-773. doi:10.1016/j.tig.2025.05.003 Manickam K, McClain MR, Demmer LA, et al. Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23(11):2029-2037. doi:10.1038/s41436-021-01242-6 Smith L, Malinowski J, Ceulemans S, et al. Genetic testing and counseling for the unexplained epilepsies: An evidence-based practice guideline of the National Society of Genetic Counselors. J Genet Couns. 2023;32(2):266-280. doi:10.1002/jgc4.1646 Rodan LH, Stoler J, Chen E, Geleske T; Council on Genetics . Genetic Evaluation of the Child With Intellectual Disability or Global Developmental Delay: Clinical Report. Pediatrics. 2025;156(1):e2025072219. doi:10.1542/peds.2025-072219Ewans LJ, Minoche AE, Schofield D, et al. Whole exome and genome sequencing in mendelian disorders: a diagnostic and health economic analysis. Eur J Hum Genet. 2022;30(10):1121-1131. doi:10.1038/s41431-022-01162-2 van de Kamp JM, Betsalel OT, Mercimek-Mahmutoglu S, et al. Phenotype and genotype in 101 males with X-linked creatine transporter deficiency. J Med Genet. 2013;50(7):463-472. doi:10.1136/jmedgenet-2013-101658 Dunbar M, Jaggumantri S, Sargent M, Stockler-Ipsiroglu S, van Karnebeek CD. Treatment of X-linked creatine transporter (SLC6A8) deficiency: systematic review of the literature and three new cases. Mol Genet Metab. 2014;112(4):259-274. doi:10.1016/j.ymgme.2014.05.011