Figure 2. Overall analytical pipeline for gene prioritization.

Pedigrees are symbolic only. Three steps were adopted to search for genes (or gene sets) that may explain HSCR families. Step 1: genes shared by two patients in the same family at the same variant site were extracted; Step2: these genes were clustered or linked to themselves, genes recurrently found with statistical support (pVAAST) and genes know to ENS development through bioinformatics analyses, within and across families; Step3: genes and gene combinations were checked for family cosegregation with the phenotype.