KIF1A is a molecular motor for membrane‐bound cargo important to the development and survival of sensory neurons. KIF1A dysfunction has been associated with several Mendelian disorders with a spectrum of overlapping phenotypes, ranging from spastic paraplegia to intellectual disability. We present a novel pathogenic in‐frame deletion in the KIF1A molecular motor domain inherited by two affected siblings from an unaffected mother with apparent germline mosaicism. We identified eight additional cases with heterozygous, pathogenic KIF1A variants ascertained from a local data lake. Our data provide evidence for the expansion of KIF1A‐associated phenotypes to include hip subluxation and dystonia as well as phenotypes observed in only a single case: gelastic cataplexy, coxa valga, and double collecting system. We review the literature and suggest that KIF1A dysfunction is better understood as a single neuromuscular disorder with variable involvement of other organ systems than a set of discrete disorders converging at a single locus.

中文翻译：

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KIF1A 相关显性疾病的表型扩展：新变体的描述和已发表病例的回顾。

KIF1A 是膜结合货物的分子马达，对感觉神经元的发育和存活很重要。KIF1A功能障碍与几种孟德尔疾病有关，这些疾病具有一系列重叠的表型，从痉挛性截瘫到智力障碍。我们在KIF1A分子运动域中提出了一种新的致病性框内缺失，该域由未受影响的母亲的两个受影响的兄弟姐妹继承，具有明显的生殖系嵌合体。我们确定了另外 8 个病例，这些病例具有从本地数据湖中确定的杂合、致病性KIF1A变异。我们的数据为KIF1A的扩增提供了证据相关的表型包括髋关节半脱位和肌张力障碍，以及仅在一个案例中观察到的表型：凝胶猝倒、髋外翻和双收集系统。我们回顾了文献，并建议将KIF1A功能障碍更好地理解为一种单一的神经肌肉疾病，其他器官系统的参与程度不同，而不是一组集中在单个位点的离散疾病。