Oh no! Virtual access to NCM Houston 2023 has ended… I did find a couple of talks that may entertain me before the rest are posted on YouTube. Tonight I watched Cate Paschal from the Seattle Children’s Hospital & University of Washington present on “Future diagnostic potential for long-read sequencing as a single assay for imprinting disorders.” They started by focusing on chromosome 15q11.2q13 region that is critical for Prader Willi syndrome (PWS) and Angelman syndrome (AS). Prader Willi can present prenatally, said Paschal. In contrast, Angelman syndrome patients have normal prenatal and birth history and then delayed progression six to twelve months. The molecular defects in PWS and AS are commonly deletions. Depending on the location of the deletion, paternal or maternal, PWS or AS will occur. Traditional testing for both of these disorders is typically challenging because it may involve microsatellite analysis and methylation PCR. Paschal described methylation PCR and bisulfite conversion. Paschal’s lab developed methylation-sensitive MLPA. The assay works “pretty well” but Paschal noted that other approaches were needed. Paschal explained a case of a two-year-old female with developmental delays. Methylation-sensitive MLPA did not identify AS. Next, a trio short read exome was performed that identified AS. Paschal wanted to use Oxford Nanopore Technologies long-read sequencing to “shorten that journey” for diagnosis. As part of a collaboration and new study, Paschal is using samples from previous testing for long-read sequence analysis. Coverage and methylation levels provided information about likely AS. In addition, two identical copies of chromosome 15 can be inferred from the data. Results for the first twenty samples provided 100% concordance with previous clinical testing! Paschal concluded that there is a potential for long-read sequencing to shorten the testing and diagnostic process for imprinting disorders. This session highlighted how complex diagnostic processes are!
