编码中心粒形成主要调节因子的PLK4基因发生突变，确定了一种原发性侏儒症的新基因座。
Mutation in PLK4, encoding a master regulator of centriole formation, defines a novel locus for primordial dwarfism.
作者信息
Shaheen Ranad, Al Tala Saeed, Almoisheer Agaadir, Alkuraya Fowzan S
机构信息
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Department of Pediatrics, Armed Forces Hospitals Programme-Southern Region, Khamis Mushayt, Saudi Arabia.
出版信息
J Med Genet. 2014 Dec;51(12):814-6. doi: 10.1136/jmedgenet-2014-102790. Epub 2014 Oct 15.
BACKGROUND
Primordial dwarfism (PD) is a heterogeneous clinical entity characterised by severe prenatal and postnatal growth deficiency. Despite the recent wave of disease gene discovery, the causal mutations in many PD patients remain unknown.
OBJECTIVE
To describe a PD family that maps to a novel locus.
METHODS
Clinical, imaging and laboratory phenotyping of a new family with PD followed by autozygosity mapping, linkage analysis and candidate gene sequencing.
RESULTS
We describe a multiplex consanguineous Saudi family in which two full siblings and one half-sibling presented with classical features of Seckel syndrome in addition to optic nerve hypoplasia. We were able to map the phenotype to a single novel locus on 4q25-q28.2, in which we identified a five base-pair deletion in PLK4, which encodes a master regulator of centriole duplication.
CONCLUSIONS
Our discovery further confirms the role of genes involved in centriole biology in the pathogenesis of PD.
背景
原始侏儒症（PD）是一种异质性临床疾病，其特征为严重的产前和产后生长发育迟缓。尽管最近发现了一波疾病基因，但许多PD患者的致病突变仍不明确。
目的
描述一个定位于新基因座的PD家系。
方法
对一个新的PD家系进行临床、影像学和实验室表型分析，随后进行纯合性定位、连锁分析和候选基因测序。
结果
我们描述了一个沙特近亲家系，其中两个全同胞和一个半同胞除视神经发育不全外，还表现出塞克尔综合征的典型特征。我们能够将该表型定位到4q25-q28.2上的一个新基因座，在该基因座中，我们在编码中心粒复制主调节因子的PLK4中鉴定出一个5个碱基对的缺失。
结论
我们的发现进一步证实了参与中心粒生物学的基因在PD发病机制中的作用。
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