Fig. 1: Identification of DSP and PPL variants by whole-exome sequencing.
From: Desmoplakin and periplakin genetically and functionally contribute to eosinophilic esophagitis
a Schema depicting the workflow for whole-exome sequencing (WES) filtering of rare variants in five patients with eosinophilic esophagitis (EoE) in the discovery set and confirmation in the replication set, as detailed in Methods. b Simplified pedigree of F430 (Details are in Supplementary Fig. 1). The arrowhead in the lower left corner indicates the proband and the slash indicates a deceased subject. “Not assessed” indicates the subject having GI symptoms but had never undergone an esophagogastroduodenoscopy. c Pedigrees of families with DSP or PPL variants in the replication set. Solid symbols indicate subjects with EoE, and open symbols indicate unaffected subjects. Arrowheads in the lower left corner indicate probands. For variant genotyping, “m” indicates the mutant DSP or PPL allele and “+” the reference allele. d Protein domain architectures and the location of amino acids predicted by mutations for DSP and PPL. The red diamond indicates a “hotspot” for mutations associated with cardiocutaneous disorders30. EoE eosinophilic esophagitis, DSP desmoplakin, PPL periplakin, AA amino acid, MAF minor allele frequency, GI gastrointestinal, NA not assessed, DSC1 desmocollin 1, JUP junction plakoglobin, PKP1 plakophilin 1, IFs intermediate filaments, EVPL envoplakin, PRD plakin repeat domain, LD linker domain.
