Improving genetic diagnosis in Mendelian disease with transcriptome sequencing
Cummings BB, Marshall JL, Tukiainen T, Lek M, Donkervoort S, Foley AR, Bolduc V, Waddell LB, Sandaradura SA, O’Grady G, Estrella E, Reddy HM, Zhao F, Weisburd B, Karczewski KJ, O’Donnell-Luria A, Birnbaum D, Sarkozy A, Hu Y, Gonorazky H, Claeys K, Joshi H, Bournazos A, Oates EC, Ghaoui R, Davis MR, Laing NG, Topf A, Consortium G, Kang PB, Beggs AH, North KN, Straub V, Dowling JJ, Muntoni F, Clarke NF, Cooper ST, Bönnemann CG, MacArthur DG. Improving genetic diagnosis in Mendelian disease with transcriptome sequencing. Science Translational Medicine 2017, 9 PMID: 28424332, PMCID: PMC5548421, DOI: 10.1126/scitranslmed.aal5209.Peer-Reviewed Original ResearchMeSH KeywordsCollagen Type VIHigh-Throughput Nucleotide SequencingHumansMuscular DiseasesMutationTranscriptomeConceptsTranscriptome sequencingRNA-seqCurrent diagnostic ratePrior genetic analysisTranscript level changesTriple-helical domainDeep intronic regionsWhole-genome sequencingSplice-altering variantsInterpretation of variantsRepeat motifsGenomic analysisHelical domainMendelian disease diagnosisGenetic analysisMendelian diseasesIntronic regionsSkeletal muscle samplesSequencingRare disease diagnosisIntronic mutationOverall diagnosis rateStandard diagnostic approachRare muscle disorderComplementary diagnostic tool