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Mutation in PLK4, encoding a master regulator of centriole formation, defines a novel locus for primordial dwarfism
  1. Ranad Shaheen1,
  2. Saeed Al Tala2,
  3. Agaadir Almoisheer1,
  4. Fowzan S Alkuraya1,3
  1. 1Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  2. 2Department of Pediatrics, Armed Forces Hospitals Programme-Southern Region, Khamis Mushayt, Saudi Arabia
  3. 3Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
  1. Correspondence to Dr Fowzan S Alkuraya, Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia; falkuraya{at}kfshrc.edu.sa

Abstract

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.

  • Seckel
  • Centriole assembly
  • autozygome

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