Diagnostic utility of transcriptome sequencing for rare Mendelian diseases.

Autor:	Lee H; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Huang AY; Institute for Precision Health, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Wang LK; Institute for Precision Health, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Yoon AJ; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Renteria G; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Eskin A; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Signer RH; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Dorrani N; Department of Pediatrics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Nieves-Rodriguez S; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Wan J; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Douine ED; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Woods JD; Department of Pediatrics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Dell'Angelica EC; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Fogel BL; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.; Department of Neurology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Martin MG; Department of Pediatrics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Butte MJ; Department of Pediatrics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.; Department of Microbiology, Immunology, and Molecular Genetics, University of California-Los Angeles, Los Angeles, CA, USA., Parker NH; Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Wang RT; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Shieh PB; Department of Neurology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Wong DA; Department of Pediatrics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Gallant N; Department of Pediatrics, School of Medicine, University of California-Irvine, Irvine, CA, USA.; Miller Children's and Women's Hospital, Long Beach, CA, USA., Singh KE; Department of Pediatrics, School of Medicine, University of California-Irvine, Irvine, CA, USA.; Miller Children's and Women's Hospital, Long Beach, CA, USA., Tavyev Asher YJ; Department of Pediatrics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.; Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Sinsheimer JS; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.; Department of Biomathematics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.; Department of Biostatistics, Fielding School of Public Health, University of California-Los Angeles, Los Angeles, CA, USA., Krakow D; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.; Department of Pediatrics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.; Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Loo SK; Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Allard P; Institute for Society and Genetics, Life Sciences, University of California-Los Angeles, Los Angeles, CA, USA., Papp JC; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Palmer CGS; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.; Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.; Institute for Society and Genetics, Life Sciences, University of California-Los Angeles, Los Angeles, CA, USA., Martinez-Agosto JA; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.; Department of Pediatrics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.; Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., Nelson SF; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA. snelson@mednet.ucla.edu.; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA. snelson@mednet.ucla.edu.; Department of Pediatrics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA. snelson@mednet.ucla.edu.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2020 Mar; Vol. 22 (3), pp. 490-499. Date of Electronic Publication: 2019 Oct 14.
DOI:	10.1038/s41436-019-0672-1
Abstrakt:	Purpose: We investigated the value of transcriptome sequencing (RNAseq) in ascertaining the consequence of DNA variants on RNA transcripts to improve the diagnostic rate from exome or genome sequencing for undiagnosed Mendelian diseases spanning a wide spectrum of clinical indications. Methods: From 234 subjects referred to the Undiagnosed Diseases Network, University of California-Los Angeles clinical site between July 2014 and August 2018, 113 were enrolled for high likelihood of having rare undiagnosed, suspected genetic conditions despite thorough prior clinical evaluation. Exome or genome sequencing and RNAseq were performed, and RNAseq data was integrated with genome sequencing data for DNA variant interpretation genome-wide. Results: The molecular diagnostic rate by exome or genome sequencing was 31%. Integration of RNAseq with genome sequencing resulted in an additional seven cases with clear diagnosis of a known genetic disease. Thus, the overall molecular diagnostic rate was 38%, and 18% of all genetic diagnoses returned required RNAseq to determine variant causality. Conclusion: In this rare disease cohort with a wide spectrum of undiagnosed, suspected genetic conditions, RNAseq analysis increased the molecular diagnostic rate above that possible with genome sequencing analysis alone even without availability of the most appropriate tissue type to assess.
Databáze:	MEDLINE
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