#apaperaday: RNA-seq analysis, targeted long-read sequencing and in silico prediction to unravel pathogenic intronic events and complicated splicing abnormalities in dystrophinopathy

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: RNA-seq analysis, targeted long-read sequencing and in silico prediction to unravel pathogenic intronic events and complicated splicing abnormalities in dystrophinopathy

Today’s pick is from human genetics by Okubo et al on discovering intronic mutations in Duchenne & Becker patients. Doi 10.1007/s00439-022-02485-2

Duchenne & Becker are most often caused by deletions or duplications of one or more exons (74%) or small mutations within an exon (25%). In 1% of cases other mutation types occur which are more challenging to find.

Here authors performed a combination of mRNA analysis and long read sequencing of DNA for 20 patients where no mutation was identified with conventional diagnostic analysis.

The authors found cryptic splicing events in 15 patients, a case of exon skipping due to a branch point mutation, 2 inversions, one large insertion and a repeat expansion in an intron. On mRNA level the cryptic splicing and exon skipping events were clear.