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Open Access 01-05-2018 | Transcriptomics

“Transcriptomics”: molecular diagnosis of inborn errors of metabolism via RNA-sequencing

Authors: Laura S. Kremer, Saskia B. Wortmann, Holger Prokisch

Published in: Journal of Inherited Metabolic Disease | Issue 3/2018

Abstract

Exome wide sequencing techniques have revolutionized molecular diagnostics in patients with suspected inborn errors of metabolism or neuromuscular disorders. However, the diagnostic yield of 25–60% still leaves a large fraction of individuals without a diagnosis. This indicates a causative role for non-exonic regulatory variants not covered by whole exome sequencing. Here we review how systematic RNA-sequencing analysis (RNA-seq, “transcriptomics”) lead to a molecular diagnosis in 10–35% of patients in whom whole exome sequencing failed to do so. Importantly, RNA-sequencing based discoveries cannot only guide molecular diagnosis but might also unravel therapeutic intervention points such as antisense oligonucleotide treatment for splicing defects as recently reported for spinal muscular atrophy.

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Title: “Transcriptomics”: molecular diagnosis of inborn errors of metabolism via RNA-sequencing
Authors: Laura S. Kremer
Saskia B. Wortmann
Holger Prokisch
Publication date: 01-05-2018
Publisher: Springer Netherlands
Published in: Journal of Inherited Metabolic Disease / Issue 3/2018
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-017-0133-4

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