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Mutation in PLK4, encoding a master regulator of centriole formation, defines a novel locus for primordial dwarfism.

Authors:
Ranad Shaheen Saeed Al Tala Agaadir Almoisheer Fowzan S Alkuraya

J Med Genet 2014 Dec 15;51(12):814-6. Epub 2014 Oct 15.

Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

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.

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http://dx.doi.org/10.1136/jmedgenet-2014-102790DOI Listing
December 2014

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