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ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6.

Authors: Zariwala, MA  Gee, HY  Kurkowiak, M  Al-Mutairi, DA  Leigh, MW  Hurd, TW  Hjeij, R  Dell, SD  Chaki, M  Dougherty, GW  Adan, M  Spear, PC  Esteve-Rudd, J  Loges, NT  Rosenfeld, M  Diaz, KA  Olbrich, H  Wolf, WE  Sheridan, E  Batten, TF  Halbritter, J  Porath, JD  Kohl, S  Lovric, S  Hwang, DY  Pittman, JE  Burns, KA  Ferkol, TW  Sagel, SD  Olivier, KN  Morgan, LC  Werner, C  Raidt, J  Pennekamp, P  Sun, Z  Zhou, W  Airik, R  Natarajan, S  Allen, SJ  Amirav, I  Wieczorek, D  Landwehr, K  Nielsen, K  Schwerk, N  Sertic, J  Kohler, G  Washburn, J  Levy, S  Fan, S  Koerner-Rettberg, C  Amselem, S  Williams, DS  Mitchell, BJ  Drummond, IA  Otto, EA  Omran, H  Knowles, MR  Hildebrandt, F 
Citation: Zariwala MA, etal., Am J Hum Genet. 2013 Aug 8;93(2):336-45. doi: 10.1016/j.ajhg.2013.06.007. Epub 2013 Jul 25.
Pubmed: (View Article at PubMed) PMID:23891469
DOI: Full-text: DOI:10.1016/j.ajhg.2013.06.007

Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function.


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CRRD Object Information
CRRD ID: 8553661
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.