부산대학교 도서관

Assimilation of atlas is a rare skeletal malformation causing nerve compression with high risk of fatal. However, the genetic etiology of assimilation of atlas AOA is currently lacking. In this paper, the whole-exome sequencing (WES) analysis was employed to study a Chinese family having a sporadic proband son of assimilation of atlas AOA but other healthy family members. We identified a novel variant in ciliary rootlet coiled-coil gene (NM_014675.5 (CROCC): c.4702C>T (r.4702c>u, p.(Arg1568Cys)). The variant had different genotypes between the proband and healthy family members but with high conservations of “damage” to protein structure based on MutationTaster and SIFT prediction. CROCC gene can be obtained in both healthy (n=220) and non-mutated assimilation of atlas AOA patient samples (n=68) but absented in five sporadic patients with the novel variant. Furthermore, abnormal of cilia was observed after editing the target sequence on CROCC using CRISPR-Cas9. These results suggested that assimilation of atlas AOA might be caused by the mutation of CROCC: c.4702C>T (r.4702c>u, p.(Arg1568Cys)). With strong amino acid conservation and interaction regulation, the variant mutation could cause the signal disorder of skeletal development which may lead to the defective bone formation and finally cause the development of assimilation of atlas AOA.