Implication of a de novo Variant in ciliary rootlet coiled- coil (CROCC) with assimilation of atlas (AOA)

  • Huaiyu Tong Department of Neurosurgery, First Medical Center, General Hospital of Chinese PLA, Beijing, China
  • Chongye Guo Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing 100101, China
  • Liang Liang Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing, China
  • Hua Mi XuanWu TCM Hospital Beijing, Beijing, China
  • Meng Li Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing 100101, China
  • Yiheng Yin Department of Neurosurgery, First Medical Center, General Hospital of Chinese PLA, Beijing, China
  • Lijun Shang School of Human Sciences, London Metropolitan University, London, N7 8DB, UK
  • Shuangli Mi Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing, China
  • Xinguang Yu Department of Neurosurgery, First Medical Center, General Hospital of Chinese PLA, Beijing, China

Abstract

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.

Published
2022-06-23
How to Cite
TONG, Huaiyu et al. Implication of a de novo Variant in ciliary rootlet coiled- coil (CROCC) with assimilation of atlas (AOA). Genetics & Applications, [S.l.], v. 6, n. 1, p. 11-26, june 2022. ISSN 2566-431X. Available at: <https://journal.genapp.ba/index.php/genapp/article/view/165>. Date accessed: 12 aug. 2022. doi: https://doi.org/10.31383/ga.vol6iss1pp11-26.
Section
Research Articles