Journal article

Multiomic analysis elucidates Complex I deficiency caused by a deep intronic variant in NDUFB10

Guy Helman, Alison G Compton, Daniella H Hock, Marzena Walkiewicz, Gemma R Brett, Lynn Pais, Tiong Y Tan, Ricardo De Paoli-Iseppi, Michael B Clark, John Christodoulou, Susan M White, David R Thorburn, David A Stroud, Zornitza Stark, Cas Simons

Human Mutation | WILEY | Published : 2020


The diagnosis of Mendelian disorders following uninformative exome and genome sequencing remains a challenging and often unmet need. Following uninformative exome and genome sequencing of a family quartet including two siblings with suspected mitochondrial disorder, RNA sequencing (RNAseq) was pursued in one sibling. Long-read amplicon sequencing was used to determine and quantify transcript structure. Immunoblotting studies and quantitative proteomics were performed to demonstrate functional impact. Differential expression analysis of RNAseq data identified significantly decreased expression of the mitochondrial OXPHOS complex I subunit NDUFB10 associated with a cryptic exon in intron 1 of ..

View full abstract


Awarded by National Human Genome Research Institute

Awarded by Medical Research Future Fund

Awarded by National Health and Medical Research Council

Funding Acknowledgements

National Human Genome Research Institute, Grant/Award Numbers: R01 HG009141, UM1 HG008900; Medical Research Future Fund, Grant/Award Number: ARG76368; National Health and Medical Research Council, Grant/Award Numbers: 1072662, 1140851, 1140906, 1155244, 1164479