Submission Details

Centrosomal protein 57kDa, also known as Translokin or TLk, encoded by CEP57 gene functions in microtubular stabilization and mediates its nuclear translocation and mitogenic activity. Mutations in this gene have been found to cause mosaic variegated aneuploidy (MVA) syndrome type 2. Snape K et al., (2011) using exome sequencing identified biallelic LoF CEP57 mutation as a cause of constitutional mosaic aneuploidies. In this article, two Mexican siblings with MVA carry the same compound heterozygous CEP57 mutations, a 2-bp deletion (520delGA) in exon 5, and an 11-bp duplication in exon 9 (915_925dup11); Another 2 individuals with biallelic CEP57 mutations, homozygous for c.341C>T;p.R81X, and c.915_925dup11, from a cohort of 13 BUB1B negative families with MVA were also identified. De La Torre-Garcia et al., (2018) identified a Mexico boy with MVA homozygous for CEP57 c.915_925dup11. Pinson L et al., (2014) found a Morocan girl from a consanguineous family homozygous for CEP57 c.915_925dup11. Brightman DS et al.(2018) found a Pakistani girl with MVA of a consanguineous family homozygous for CEP57 c.697delA, p.Lys235Argfs*31). Experimental evidences showed CEP57 protein is localized to kinetochore contributing spindle microtubule organization, CEP57 depletion leads to missegregation of chromosome. siRNA resistant Cep57 wt with mutated siRNA targeted region in HeLa cells rescued the phenotypes. Research on CEP57 gene function in microtubule stability has been upheld over time. In summary, there have been sufficient evidences supporting the association of CEP57 with autosomal recessive inherited Mosaic Variegated Aneuploidy (MVA) type 2.