PMC:4157146 / 6537-7679 JSONTXT

{"project":"2_test","denotations":[{"id":"25192045-23796196-2045865","span":{"begin":189,"end":191},"obj":"23796196"}],"text":"Although much progress in gene identification for PCD has been achieved, it has been recently estimated that the known genes in which mutations cause PCD account for about 65% of PCD cases.40 Therefore, we employed a next-generation sequencing (NGS) approach for linkage mapping and variant identification in order to identify additional PCD-causing mutations. This analysis revealed loss-of-function mutations in CCDC151 in three unrelated families characterized by PCD with specific loss of the ODAs. By analyzing CCDC151-deficient human cells, mice, and zebrafish, we show a requirement for CCDC151 in the correct establishment of left-right asymmetry because loss of CCDC151 function is associated with the randomization of visceral organ positioning. A severe reduction of CCDC151 occurs in the axonemes of nasal respiratory cilia of individuals carrying CCDC151 nonsense mutations, which disrupts assembly of both the ODAs and the ODA targeting and docking components CCDC114 and ARMC4 into axonemes. These results highlight the essential role of CCDC151 in the specification of ciliary motility during human and vertebrate development."}