Mutational analysis. (A) Schematic representation of PIEZO1 (blue squares, exons; horizontal double lines, introns; double slashes, large introns); red arrows indicate exonic positions of the nucleotides mutated in the 7 families in whom DHSt was previously mapped to chromosome 16q. (B) A 2-dimensional (2D) hydropathy profile of human PIEZO1 protein. The transmembrane regions of PIEZO1 (UniProt accession Q92508) predicted by TMHMM were displayed using TMRPres2D. Red circles mark approximate locations of DHSt-associated missense mutations. (C) Evolutionary conservation of the residues mutated in our DHSt patients (red-shaded boxes) among the species indicated at left.