(A) Summary of clinical phenotypes in affected individuals with UPF2 variants. R, right; AVSD, atrioventricular septal defect; ASD, autism spectrum disorder; N, not present; Y, present; avg, average; ext, extremely; artic, articulation disorder; mod, moderate; NA, not available because the child has severe ID and is non-verbal.
(B) cDNA Sanger sequencing of a lymphoblastoid cell line (LCL) from case 1 (top panel) and a control LCL (bottom panel) across the site of the c.1940 (NM_080599) deletion. The background “noise” in the case 1 sequencing panel is due to the overlapping frameshifted c.1940delA mRNA, which is not 100% degraded by NMD.
(C) Western blot analysis revealed that individuals with UPF2 variants exhibit a reduction in UPF2 protein levels (n = 6 control, n = 1 c.1940delA/case 1, n = 1 UPF2 CNV/case 3, n = 2 UPF2 CNV).
(D) A significant positive correlation was observed when differentially expressed genes (DEGs) were compared between unrelated individuals carrying mutations in different core NMD factor mutations (n = 1 c.1940delA/case 1, n = 1 UPF2 CNV/case 3, n = 2 UPF2 CNV grouped, n = 3 UPF3B mutations).
Error bars represent mean ± SEM.
See also Figures S1 and S2.