title: Mutation in PLK4, encoding a master regulator of centriole formation, defines a novel locus for primordial dwarfism.
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.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Ranad
authors.initials: R
authors.lastname: Shaheen
authors.affiliation: Department of Pediatrics, Armed Forces Hospitals Programme-Southern Region, Khamis Mushayt, Saudi Arabia.
authors.forename: Saeed
authors.initials: S
authors.lastname: Al Tala
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Agaadir
authors.initials: A
authors.lastname: Almoisheer
authors.affiliation: 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.
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D002502:Centrioles / Q000235:genetics*; D002675:Child, Preschool; D002874:Chromosome Mapping; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004392:Dwarfism / Q000175:diagnosis / Q000235:genetics*; D019066:Facies; D005260:Female; D023061:Gene Order; D006801:Humans; D007223:Infant; D008297:Male; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D040641:Quantitative Trait Loci
chemical_list: C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Centriole assembly; Seckel; autozygome