WFS1 and Wolfram syndrome: The heterozygous truncation variant of WFS1 was not considered to be dominant pathogenic for Wolfram syndrome 1 for the following reasons: (i) heterozygous truncation variants were also present in healthy individuals (father of F152:II-1 and father of F147:II-1) and in-house healthy normal controls; (ii) truncating variants of WFS1 were frequently seen in the gnomAD database but were not clustered in patients with HON (Supplementary Fig. 9); and (iii) the Loss Intolerance probability (pLI) for WFS1 was zero.