Whole Genome Sequence Identifies the Second Allele: An Intronic Variant in RYR1 Contributes to Early-Onset Fetal Akinesia Deformation Sequence

This study highlights the utility of WGS in diagnosing fetal anomalies with negative WES results by identifying noncoding and structural variants. The identification of novel <i>RYR1</i> mutations broadens the genetic spectrum of recessive CMs and emphasizes the necessity for functional assays to accurately interpret intronic variants. WGS is recommended for cases of recurrent fetal anomalies when WES is inconclusive, although careful interpretation of variants is advised.