PT  - JOURNAL ARTICLE
AU  - Ranad Shaheen
AU  - Saeed Al Tala
AU  - Agaadir Almoisheer
AU  - Fowzan S Alkuraya
TI  - Mutation in <em>PLK4</em>, encoding a master regulator of centriole formation, defines a novel locus for primordial dwarfism
AID  - 10.1136/jmedgenet-2014-102790
DP  - 2014 Dec 01
TA  - Journal of Medical Genetics
PG  - 814--816
VI  - 51
IP  - 12
4099  - http://jmg.bmj.com/content/51/12/814.short
4100  - http://jmg.bmj.com/content/51/12/814.full
SO  - J Med Genet2014 Dec 01; 51
AB  - 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.