Locations of WRN mutations. Exons are designated as boxes 1–35. Introns are indicated by thin lines. The numbers above the exons indicate the nucleotide positions in the WRN cDNA (GenBank accession no. L76937.) with the first ATG being 1. The localizations of the functional domains are indicated. Purple boxes, exonuclease domain; yellow boxes, helicase domain; green boxes, RQC, the RecQ helicase conserved region; pink boxes, HRDC, the Helicase, RnaseD, C-terminal conserved region; and gray box, NLS, the nuclear localization signal; CDS, coding sequence; FS/Ter, frameshift and premature translation termination; IVS, intervening sequence. I-VI indicate the motifs in exonuclease and helicase domains.