Unlike genetic tests that analyze one gene or small groups of related genes at a time, a recently developed test, called whole-exome sequencing (WES), analyzes the portion of the genome made up of exons – functionally important regions of DNA that direct the production of proteins.

Collectively, these regions are called the exome. The human genome contains about 180,000 exons arranged in about 20,000 genes. Most single gene disorders arise from errors in the exome. Since clinical laboratories began offering WES in the last two years, clinicians have increased its use significantly. Many patients with rare disorders who spent years on uninformative diagnostic odysseys enduring costly, time consuming, and sometimes invasive procedures have now received definitive diagnoses through WES.

Most single gene disorders arise from errors in the exome.

A group of pediatric researchers and clinical geneticists at CUMC evaluated the feasibility and clinical usefulness of whole-exome sequencing in 115 patients, most of them children. Their report, published in the journal Genetics in Medicine, shows that the most common indications for WES are birth defects (24.3 percent) and developmental delay (25.2 percent). Once they established a diagnosis with WES, they were able to discontinue additional planned testing in all patients.

WES enabled clinicians to screen for additional manifestations in eight patients, to alter the management of 14 patients, provide novel therapy to two, identify other familial mutation carriers in five, and provide reproductive planning to six. They concluded that “whole-exome sequencing is feasible, significantly improves our diagnostic ability, and allows timely medical interventions, informed reproductive choices, and avoidance of additional testing.”