The identification of a novel CCNQ gene tail extension variant contributing to syndactyly, telecanthus and anogenital and renal malformations syndrome

Abstract The “toe syndactyly, telecanthus and anogenital and renal malformations” (STAR) syndrome is a rare X‐linked dominant inherited kidney ciliopathy caused by CCNQ gene mutations. Here, we investigated the genotype and phenotype in the first two twin sisters with a novel tail extension CCNQ variant in Asia. Genetic variants of the pedigree were screened using whole‐exome sequence analysis and validated by direct Sanger sequencing. The genetic function was investigated through cultured cells and zebrafish embryos transfected with mutant. The proband is suffered from end‐stage renal disease, telecanthus, scoliosis, anal atresia, bilateral hydronephrosis pyeloureter dilation and hearing loss, while her twin sister had milder phenotypes. A novel heterozygous variant c.502_518delinsA (p.Val168SerfsTer173) in CCNQ gene was identified in the twins and their asymptomatic mosaic mother. The concurrent deletion of 17 bases and insertion of one base variant led to the loss of 5 amino acids, subsequently caused a 96 more amino acids tail extension delaying the appearance of stop codon. The loss‐of‐function variant of CCNQ not only led to the impaired expression of cyclin M but also increased the binding affinity of CDK10‐cyclin M complex, which is different from the previous study. The research expanded the genotypic and phenotypic spectrum of STAR syndrome.