Development and Implementation of a Novel Comprehensive Panel for the Early Detection of Angelman Syndrome

A classic phenotype of AS has been described which includes developmental delay, intellectual disability, speech impairment, gait ataxia and a happy demeanor. However, these features are not apparent in infancy. Further, initial symptoms of developmental delay are non-specific, which often complicate a diagnosis. The underlying molecular mechanism of AS is complex, and is known to be caused by methylation defects, deletions, and pathogenic single nucleotide variants in UBE3A, currently requiring multiple clinical tests to access. Taken together, despite the prevalence of AS, many patients do not receive a timely molecular diagnosis, may receive an incorrect diagnosis, or receive no diagnosis at all.

As precision therapeutics are increasingly developed, including ASOs which have shown tremendous promise in animal models, receiving a molecular diagnosis becomes exponentially more important. This project will address the current limitations of diagnostic testing for AS by utilizing a novel long read (LR) based sequencing approach, capturing multiple disease categories and variant types in a single economical test.