Mutations in CEP57 cause mosaic variegated aneuploidy syndrome

Abstract

Using exome sequencing and a variant prioritization strategy that focuses on loss-of-function variants, we identified biallelic, loss-of-function CEP57 mutations as a cause of constitutional mosaic aneuploidies. CEP57 is a centrosomal protein and is involved in nucleating and stabilizing microtubules. Our findings indicate that these and/or additional functions of CEP57 are crucial for maintaining correct chromosomal number during cell division.

Figure 1

CEP57 structure, mutations and resulting aneuploidy (a) Aneuploid metaphase karyotypes from family 633, showing gains and losses of whole chromosomes. (b) Schematic representation of the genomic structure of CEP57 with the positions of mutations indicated with arrows. Below is the protein structure showing the coiled-coil domains, the centrosomal localisation region and microtubular stabilisation region.