AFF2 and hereditary disease: However, since the X-linked mode of inheritance had been proposed for Roifman Syndrome, we additionally investigated X-chromosome variants found in only one of the two siblings; they either did not have any known implication in human genetic disorders or mouse abnormal phenotypes (genes ARSH and HS6ST2-AS1), or they had modest protein-damaging potential and insufficient match to Roifman Syndrome phenotype (genes AFF2 and SH3KBP1, for more details see Supplementary Data 1, Supplementary Tables 3–5 and Supplementary Note 2).