ANK3 encodes multiple isoforms of ankyrin-G, resulting in variegated tissue expression and function, especially regarding its role in neuronal development. Based on the zygosity, location, and type, ANK3 variants result in different neurodevelopmental phenotypes. Autism spectrum disorder has been associated with heterozygous missense variants in ANK3, whereas a more severe neurodevelopmental phenotype is caused by isoform-dependent, autosomal-dominant, or autosomal-recessive loss-of-function variants. Here, we present four individuals affected by a variable neurodevelopmental phenotype harboring a heterozygous frameshift or nonsense variant affecting all ANK3 transcripts. Thus, we provide further evidence of an isoform-based phenotypic continuum underlying ANK3-associated pathologies and expand its phenotypic spectrum.

ANK3编码锚蛋白-G 的多种亚型，导致组织表达和功能多样化，尤其是在其在神经元发育中的作用。基于接合性、位置和类型，ANK3变体导致不同的神经发育表型。自闭症谱系障碍与ANK3中的杂合错义变异有关，而更严重的神经发育表型是由同种型依赖性、常染色体显性或常染色体隐性功能丧失变异引起的。在这里，我们展示了四个受可变神经发育表型影响的个体，这些个体具有影响所有ANK3的杂合移码或无义变体成绩单。因此，我们提供了基于同种型的表型连续体的进一步证据，该连续体是 ANK3相关病理的基础，并扩展了其表型谱。