학술논문
Clinical Exome Sequencing for Genetic Identification of Rare Mendelian Disorders
Document Type
article
Author
Lee, Hane; Deignan, Joshua L; Dorrani, Naghmeh; Strom, Samuel P; Kantarci, Sibel; Quintero-Rivera, Fabiola; Das, Kingshuk; Toy, Traci; Harry, Bret; Yourshaw, Michael; Fox, Michelle; Fogel, Brent L; Martinez-Agosto, Julian A; Wong, Derek A; Chang, Vivian Y; Shieh, Perry B; Palmer, Christina GS; Dipple, Katrina M; Grody, Wayne W; Vilain, Eric; Nelson, Stanley F
Source
JAMA. 312(18)
Subject
Language
Abstract
ImportanceClinical exome sequencing (CES) is rapidly becoming a common molecular diagnostic test for individuals with rare genetic disorders.ObjectiveTo report on initial clinical indications for CES referrals and molecular diagnostic rates for different indications and for different test types.Design, setting, and participantsClinical exome sequencing was performed on 814 consecutive patients with undiagnosed, suspected genetic conditions at the University of California, Los Angeles, Clinical Genomics Center between January 2012 and August 2014. Clinical exome sequencing was conducted as trio-CES (both parents and their affected child sequenced simultaneously) to effectively detect de novo and compound heterozygous variants or as proband-CES (only the affected individual sequenced) when parental samples were not available.Main outcomes and measuresClinical indications for CES requests, molecular diagnostic rates of CES overall and for phenotypic subgroups, and differences in molecular diagnostic rates between trio-CES and proband-CES.ResultsOf the 814 cases, the overall molecular diagnosis rate was 26% (213 of 814; 95% CI, 23%-29%). The molecular diagnosis rate for trio-CES was 31% (127 of 410 cases; 95% CI, 27%-36%) and 22% (74 of 338 cases; 95% CI, 18%-27%) for proband-CES. In cases of developmental delay in children (