NCM 2023 Houston: Future diagnostic potential for long-read sequencing as a single assay for imprinting disorders

Standard clinical genetic testing for individuals with a suspected imprinting disorder, such as Prader Willi syndrome (PWS) or Angelman syndrome (AS), typically involves multiple assays performed sequentially and can take months to years to complete. Because long-read sequencing (LRS) data can be analyzed for copy number variation, single nucleotide and indel variants, structural variants, and differences in methylation, we hypothesized that it would have high concordance to standard testing. Anonymized samples with previous clinical results for PWS or AS were selected for whole genome LRS on an Oxford Nanopore Technologies PromethION device. Reports with copy number state, methylation pattern, and pattern of single nucleotide variants for the relevant region of chromosome 15 were independently reviewed. The genetic defect was correctly identified in all 15 samples. LRS shows potential future utility as an efficient diagnostic tool for suspected imprinting disorders.