Fig. 1

 A schematic overview of the WFS1 protein, pedigrees of the three families, the audio-logical phenotypes of affected probands, and Sanger sequencing traces of the WFS1 variants. (A) Pedigrees of three families with WFS1 heterozygous variants and associated audiograms. (B) Physical map of WFS1, which contains nine transmembrane domains and an ER-luminal domain. The domains are represented as in the Universal Protein Resource (UniProt) database. The novel frameshift variant in SH486 (c.1544_1545insA:p.Phe515LeufsTer28) and the missense variant in SH550 andSH592 (c.2051 C > T:p.Ala684Val) reside in TM domain 6 and the ER-luminal domain, respectively. Conservation of the corresponding residues between species is depicted. (C) Sanger chromatogram of the respective WFS1 heterozygous variants. All probands were confirmed as de novo occurrences