Expansion of long-read genome sequencing for the molecular diagnosis of neurodevelopmental disorders and multiple congenital anomalies

Exome and genome sequencing (ES/GS) have proven to be effective tools for the diagnosis of rare disorders, including neurodevelopmental disorders (NDDs), and multiple congenital anomalies (MCA), many of which are due to highly penetrant, often de novo, variation. However, while discovery power and diagnostic yield of genomic testing have consistently improved over time, most cases of NDD/MCAs cannot be attributed to currently detectable genetic variation. We have recently applied long-reads produced using the Pacific Biosciences circular consensus sequence (CCS) technology to unsolved cases.