Mutation in PLK4, encoding a master regulator of centriole formation, defines a novel locus for primordial dwarfism
- J Med Genet. 2014 Dec;51(12):814-6. doi: 10.1136/jmedgenet-2014-102790.
- 1. Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
- 2. Department of Pediatrics, Armed Forces Hospitals Programme-Southern Region, Khamis Mushayt, Saudi Arabia.
- 3. 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.