2. Academic Validation
  3. ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6

ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6

  • Am J Hum Genet. 2013 Aug 8;93(2):336-45. doi: 10.1016/j.ajhg.2013.06.007.
Maimoona A Zariwala 1,  Heon Yung Gee,  Małgorzata Kurkowiak,  Dalal A Al-Mutairi,  Margaret W Leigh,  Toby W Hurd,  Rim Hjeij,  Sharon D Dell,  Moumita Chaki,  Gerard W Dougherty,  Mohamed Adan,  Philip C Spear,  Julian Esteve-Rudd,  Niki T Loges,  Margaret Rosenfeld,  Katrina A Diaz,  Heike Olbrich,  Whitney E Wolf,  Eamonn Sheridan,  Trevor F C Batten,  Jan Halbritter,  Jonathan D Porath,  Stefan Kohl,  Svjetlana Lovric,  Daw-Yang Hwang,  Jessica E Pittman,  Kimberlie A Burns,  Thomas W Ferkol,  Scott D Sagel,  Kenneth N Olivier,  Lucy C Morgan,  Claudius Werner,  Johanna Raidt,  Petra Pennekamp,  Zhaoxia Sun,  Weibin Zhou,  Rannar Airik,  Sivakumar Natarajan,  Susan J Allen,  Israel Amirav,  Dagmar Wieczorek,  Kerstin Landwehr,  Kim Nielsen,  Nicolaus Schwerk,  Jadranka Sertic,  Gabriele Köhler,  Joseph Washburn,  Shawn Levy,  Shuling Fan,  Cordula Koerner-Rettberg,  Serge Amselem,  David S Williams,  Brian J Mitchell,  Iain A Drummond,  Edgar A Otto,  Heymut Omran,  Michael R Knowles,  Friedhelm Hildebrandt
Affiliations

Affiliation

  • 1 Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
PMID: 23891469 DOI: 10.1016/j.ajhg.2013.06.007
Abstract

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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