Fig. 2

A Variant-specific pathophysiological mechanisms of AFF3. Schematic summary of the different type of AFF3 identified variants, their mode of inheritance, postulated mechanisms, and associated clinical phenotypes (see text for details). The number of patients we identified in each category and their identifiers are indicated. All symptoms are reported in Tables S1 and S2. Filled form = KINSSHIP syndrome, Half-filled form = milder syndrome, Form with included filled disk = more severe syndrome associated with semi-dominance, Question mark = possible association warranting further investigation. B Summary of in vivo and in vitro experiments. Schematic summary of traits associated with diminished expression and increased stabilization of AFF3 in mouse, zebrafish, HEK293 human cell, and affected individuals. The results previously published in Voisin et al., AJHG 2021 [11] are in blue, while results of this report are in black. The p.(A233T) variant is the most common de novo KINSSHIP variant [11], while the p.(M238T) and p.(M238V) variants described in this report present a milder phenotype (see text for details). Abbreviations: DD, developmental disorder; del, deletion; dup, duplication; ex, exon, ID, intellectual disability; LoF, loss-of-function; + , wild-type allele