ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6

Research output: Contribution to journalArticlepeer-review

  • Maimoona A. Zariwala
  • 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
  • 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
Original languageEnglish
Pages (from-to)336-345
Number of pages10
JournalAmerican Journal of Human Genetics
Issue number2
Early online date25 Jul 2013
Publication statusPublished - 8 Aug 2013
Externally publishedYes
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.

External organisations

  • University of North Carolina at Chapel Hill
  • Boston Children's Hospital
  • Münster University Hospital
  • Polish Academy of Sciences
  • Kuwait University
  • University of Edinburgh
  • University of Toronto
  • Massachusetts General Hospital
  • Washington University in St. Louis
  • St James's University Hospital
  • University of Colorado
  • National Institute of Allergy and Infectious Diseases
  • Concord Repatriation General Hospital
  • Yale University
  • Bar-IIan University
  • Universität Duisburg-Essen
  • Evangelisches Klinikum Bethel
  • Copenhagen University Hospital
  • Hannover Medical School
  • University of Zagreb
  • University of Michigan
  • HudsonAlpha Institute for Biotechnology
  • Ruhr-Universität Bochum
  • Institut national de la santé et de la recherche médicale
  • Université Pierre-et-Marie-Curie
  • Harvard University
  • Howard Hughes Medical Institute
  • International Institute of Molecular and Cell Biology in Warsaw
  • Northwestern University
  • University of California, Los Angeles
  • University of Leeds

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