Pathogenic variants within PAX6 are most often associated with aniridia, but have been linked with other phenotypes such as nystagmus, cataracts and foveal hypoplasia. Data are presented from a large cohort of 434 probands referred for PAX6 diagnostic testing. This analysis identified a wide range of pathogenic variants (n = 145) in 254 probands (including 61 novel variants). Excluding missense variants predicted to affect splicing, all 29 of the remaining missense variants were located within the paired (n = 27) or homeobox (n = 2) domains of the PAX6 protein, providing further evidence that these domains are critical to normal PAX6 function. Genotype-phenotype evidence suggests that while aniridia is associated with most variant types, a much broader clinical spectrum is seen in patients harbouring a missense variant, or a frameshift or run-on variant that results in an elongated or extended PAX6 protein.

PAX6内的致病变异最常与虹膜异色症相关，但已与其他表型（如眼球震颤，白内障和中央凹发育不全）联系在一起。数据来自针对PAX6的434个先证者的大量队列诊断测试。这项分析确定了254个先证者（包括61个新变异）中的多种致病变异（n = 145）。除预计会影响剪接的错义变体外，其余所有29个错义变体均位于PAX6蛋白的配对（n = 27）或同源框（n = 2）域内，提供了进一步的证据表明这些域对正常的PAX6功能至关重要。基因型-表型的证据表明，尽管无虹膜症与大多数变异类型有关，但在携带错义变异，移码或连续变异的患者中，PAX6蛋白变长或变长的患者的临床范围更广。