Panel A: Pedigree charts for seven families with patients having severe allergic disease. Each family is labeled from A to G. Filled symbols represent affected individuals, unfilled symbols represent unaffected individuals, half-filled symbols represent heterozygous unaffected individuals, and diamond symbols represent unspecified sex. Each family member is labeled with their OSMR variant status. Panel B: Schematic of the OSMR protein domains. Panel C: Table includes cDNA position, protein position, and predictions from in silico tools like CADD, SIFT, and PolyPhen-2.
10 patients with severe allergic disease and OSMR variants. (A) Family pedigrees of the 10 patients from seven different families. Filled symbols = affected individuals; unfilled symbols = unaffected individuals; half-filled symbols = heterozygous unaffected individuals; diamond symbol = unspecified sex. (B) Schematic illustrating the protein domains of OSMRβ. The amino acid locations of the two missense and four premature stop variants are shown in red. The region surrounding the missense variants (p.Ala349Asp and p.Val436Asp) was aligned with sequences from other species and found to be evolutionarily conserved. (C) LOF OSMR variants reported in patients. To our knowledge, only the p.Val436Asp variant is reported for homozygous carriers in gnomAD (https://gnomad.broadinstitute.org/), a large population database. The following in silico tools predicted the OSMR LOF variants to be damaging: Combined Annotation Dependent Depletion (CADD) (https://cadd.gs.washington.edu/), Sorting Intolerant from Tolerant (SIFT) (https://siftdna.org/), and Polymorphism Phenotyping v2 (PolyPhen-2) (https://bio.tools/polyphen-2). SIFT and PolyPhen-2 cannot be applied to premature stop and frameshift variants.