Affiliation:
1. International Peace Maternity and Child Health Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology Shanghai Jiao Tong University School of Medicine Shanghai China
2. National Human Genetic Resources Center National Research Institute for Family Planning Beijing China
Abstract
AbstractJoubert syndrome (JBTS) is a systematic developmental disorder mainly characterized by a pathognomonic mid‐hindbrain malformation. All known JBTS‐associated genes encode proteins involved in the function of antenna‐like cellular organelle, primary cilium, which plays essential roles in cellular signal transduction and development. Here, we identified four unreported variants in ARL13B in two patients with the classical features of JBTS. ARL13B is a member of the Ras GTPase family and functions in ciliogenesis and cilia‐related signaling. The two missense variants in ARL13B harbored the substitutions of amino acids at evolutionarily conserved positions. Using model cell lines, we found that the accumulations of the missense variants in cilia were impaired and the variants showed attenuated functions in ciliogenesis or the trafficking of INPP5E. Overall, these findings expanded the ARL13B pathogenetic variant spectrum of JBTS.
Funder
National Natural Science Foundation of China
Subject
Cell Biology,Clinical Biochemistry,Physiology