TY - JOUR
T1 - ARMC4 mutations cause primary ciliary dyskinesia with randomization of left/right body asymmetry
AU - Hjeij, Rim
AU - Lindstrand, Anna
AU - Francis, Richard
AU - Zariwala, Maimoona A.
AU - Liu, Xiaoqin
AU - Li, You
AU - Damerla, Rama
AU - Dougherty, Gerard W.
AU - Abouhamed, Marouan
AU - Olbrich, Heike
AU - Loges, Niki T.
AU - Pennekamp, Petra
AU - Davis, Erica E.
AU - Carvalho, Claudia M B
AU - Pehlivan, Davut
AU - Werner, Claudius
AU - Raidt, Johanna
AU - Köhler, Gabriele
AU - Häffner, Karsten
AU - Reyes-Mugica, Miguel
AU - Lupski, James R.
AU - Leigh, Margaret W.
AU - Rosenfeld, Margaret
AU - Morgan, Lucy C.
AU - Knowles, Michael R.
AU - Lo, Cecilia W.
AU - Katsanis, Nicholas
AU - Omran, Heymut
PY - 2013/8/8
Y1 - 2013/8/8
N2 - The motive forces for ciliary movement are generated by large multiprotein complexes referred to as outer dynein arms (ODAs), which are preassembled in the cytoplasm prior to transport to the ciliary axonemal compartment. In humans, defects in structural components, docking complexes, or cytoplasmic assembly factors can cause primary ciliary dyskinesia (PCD), a disorder characterized by chronic airway disease and defects in laterality. By using combined high resolution copy-number variant and mutation analysis, we identified ARMC4 mutations in twelve PCD individuals whose cells showed reduced numbers of ODAs and severely impaired ciliary beating. Transient suppression in zebrafish and analysis of an ENU mouse mutant confirmed in both model organisms that ARMC4 is critical for left-right patterning. We demonstrate that ARMC4 is an axonemal protein that is necessary for proper targeting and anchoring of ODAs.
AB - The motive forces for ciliary movement are generated by large multiprotein complexes referred to as outer dynein arms (ODAs), which are preassembled in the cytoplasm prior to transport to the ciliary axonemal compartment. In humans, defects in structural components, docking complexes, or cytoplasmic assembly factors can cause primary ciliary dyskinesia (PCD), a disorder characterized by chronic airway disease and defects in laterality. By using combined high resolution copy-number variant and mutation analysis, we identified ARMC4 mutations in twelve PCD individuals whose cells showed reduced numbers of ODAs and severely impaired ciliary beating. Transient suppression in zebrafish and analysis of an ENU mouse mutant confirmed in both model organisms that ARMC4 is critical for left-right patterning. We demonstrate that ARMC4 is an axonemal protein that is necessary for proper targeting and anchoring of ODAs.
UR - http://www.scopus.com/inward/record.url?scp=84881668924&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2013.06.009
DO - 10.1016/j.ajhg.2013.06.009
M3 - Article
C2 - 23849778
AN - SCOPUS:84881668924
SN - 0002-9297
VL - 93
SP - 357
EP - 367
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 2
ER -