Autosomal recessive microcephaly and chorioretinopathy (MCCRP) is a neurodevelopmental disorder characterized by delayed psychomotor development, growth retardation with dwarfism, and ocular abnormalities, and its occurrence has been found to be closely related to variants of the gene encoding centrosomes. However, the association between centrosomal duplication defects and the etiology of microcephaly syndromes is poorly understood. It is well known that polo-like kinase 4 (PLK4) is a key regulator of centriole duplication, and the abnormalities of centrosomal function caused by its protein variation need to be further explored in the pathogenesis of microcephaly. In our study, we found that a patient with microcephaly and chorioretinopathy harbored compound heterozygous missense variants NM_014264.4: c.2221C > T (p.Gln741*) and NM_014264.4: c.2062 T > C (p.Tyr688His) in the PLK4 gene. Overexpression experiments of the variant PLK4 proteins then showed that the G741 variant rather than the T688H variant had lost centrosomal amplification ability, and the G741 variant but not the T688H variant induced centrosomal replication disorder, which further inhibited cell proliferation, cycle division and cytoskeleton morphology in HeLa cells. Moreover, the overexpression of the two variant proteins had inconsistent effects on the target protein PLK4 by western blot analysis, also indicating that T688H variant overexpression is not functionally equivalent to WT-PLK4 overexpression. Therefore, all data support the idea that the PLK4 mutation induces centriolar duplication disorder and reduces the efficiency of mitosis inducing cell death or cell proliferation in the etiology of microcephaly disorder.

常染色体隐性小头畸形和脉络膜视网膜病变（MCCRP）是一种以精神运动发育迟缓、生长迟缓伴侏儒症和眼部异常为特征的神经发育障碍，其发生与编码中心体的基因变异密切相关。然而，人们对中心体重复缺陷与小头畸形综合征病因之间的关系知之甚少。众所周知，polo样激酶4（PLK4）是中心粒复制的关键调节因子，其蛋白变异引起的中心体功能异常需要在小头畸形发病机制中进一步探索。在我们的研究中，我们发现一名患有小头畸形和脉络膜视网膜病变的患者携带复合杂合错义变体 NM_014264.4：c.2221C > T (p.Gln741*) 和 NM_014264.4：c。PLK4 基因中的 2062 T > C (p.Tyr688His)。PLK4变体蛋白的过表达实验表明，G741变体而不是T688H变体失去了中心体扩增能力，G741变体而不是T688H变体诱导中心体复制障碍，进一步抑制细胞增殖、周期分裂和细胞骨架形态。海拉细胞。此外，通过蛋白质印迹分析，两种变体蛋白的过表达对靶蛋白 PLK4 的影响不一致，也表明 T688H 变体过表达在功能上不等同于 WT-PLK4 过表达。所以，