Triple mosaic variants of PURA in a patient with multiple congenital anomalies

In monogenic diseases, double mosaic variants of the same gene have rarely been identified. Here, we report the case of triple mosaic variants in PURA, a gene responsible for a neurodevelopmental syndrome (OMIM# 616158). Whole-exome sequencing identified three somatic PURA variants in our case with a similar neurodevelopmental syndrome: NM_005859.5: c.222C>A p.(Tyr74*), c.224T>A p.(Leu75Gln), and c.233A>G p.(Lys78Arg). The two missense variants were on the same sequence read, but the nonsense variant was not. To determine the origin of the alleles, we performed long-read sequencing because of the absence of informative SNPs near the somatic variants. Long-read sequencing revealed that these three somatic variants are derived from the same chromosome. The exact mechanism behind their occurrence is unclear, but the nonsense variant could have occurred de novo as a germline event and incomplete post-zygotic rescue for the germline variant could have led to the two missense variants.