In addition to deletions, HMGB1 frameshift variants with a putative loss-of-function effect have been identified in patients with clinical features of the 13q12.3 microdeletion syndrome [3, 13], supporting the etiological contribution of HMGB1 haploinsufficiency to the pathogenesis of the 13q12.3 microdeletion syndrome. The gene discussed is HMGB1; the disease is Down syndrome.