Functional Characterization of biallelic mutations of Centrobin as causative of Seckel-like syndrome

Seckel syndrome is a rare autosomal recessive condition characterized by intrauterine growth restriction, postnatal short stature, microcephaly, and distinctive facial features with a prominent nose. Genetic factors including nine different genes have been associated with Seckel syndrome (ATR, CENPJ, CEP63, CEP152, DNA2, NIN, NSMCE2, RBBP8, and TRAIP). However, a direct genotype-phenotype association is challenging with Seckel. Therefore, underlying the causes of this condition in general will aid in understanding the biological mechanisms. Through whole exome sequencing, we recently identified novel variants of the gene CNTROB and appears to be a candidate gene associated with the disease. The affected individuals display a similar phenotype to Seckel-like syndrome. Centrobin encoded by CNTROB is a bona fide component of centrosome and its function goes beyond centrosome: centriole associated protein. We aim to functionally characterize biallelic variants of CNTROB gene. It encodes a protein known to be involved in centriole duplication, cytokinesis and cellular proliferation. We hypothesis that this novel variants in this gene is causative of Seckel-like syndrome in humans. This would be the first study to prove the association of CNTROB gene with human disease.