Immunofluorescence Analysis and Diagnosis of Primary Ciliary Dyskinesia with Radial Spoke Defects

American Journal of Respiratory Cell and Molecular Biology
Adrien FrommerHeymut Omran

Abstract

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder caused by several distinct defects in genes responsible for ciliary beating, leading to defective mucociliary clearance often associated with randomization of left/right body asymmetry. Individuals with PCD caused by defective radial spoke (RS) heads are difficult to diagnose owing to lack of gross ultrastructural defects and absence of situs inversus. Thus far, most mutations identified in human radial spoke genes (RSPH) are loss-of-function mutations, and missense variants have been rarely described. We studied the consequences of different RSPH9, RSPH4A, and RSPH1 mutations on the assembly of the RS complex to improve diagnostics in PCD. We report 21 individuals with PCD (16 families) with biallelic mutations in RSPH9, RSPH4A, and RSPH1, including seven novel mutations comprising missense variants, and performed high-resolution immunofluorescence analysis of human respiratory cilia. Missense variants are frequent genetic defects in PCD with RS defects. Absence of RSPH4A due to mutations in RSPH4A results in deficient axonemal assembly of the RS head components RSPH1 and RSPH9. RSPH1 mutant cilia, lacking RSPH1, fail to assemble RSPH9, whereas ...Continue Reading

References

Apr 2, 2003·Human Molecular Genetics·Inés Ibañez-TallonHeymut Omran
Dec 3, 2003·Cell Motility and the Cytoskeleton·Elizabeth F Smith, Pinfen Yang
Mar 8, 2005·American Journal of Respiratory and Critical Care Medicine·Manfred FliegaufHeymut Omran
Jul 7, 2005·The Journal of Cell Biology·Gregory J PazourGeorge B Witman
Mar 2, 2006·Journal of Cell Science·Pinfen YangGeorge B Witman
Oct 25, 2006·Annual Review of Physiology·Maimoona A ZariwalaHeymut Omran
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Bénédicte DuriezSerge Amselem
Dec 5, 2008·Nature·Heymut OmranHiroyuki Takeda
Dec 1, 2009·American Journal of Human Genetics·Niki Tomas LogesHeymut Omran
Feb 20, 2010·American Journal of Respiratory and Critical Care Medicine·June K MarthinKim G Nielsen
Jan 1, 2009·Methods in Cell Biology·Heymut Omran, Niki T Loges
Jun 10, 2010·The European Respiratory Journal·C E KuehniUNKNOWN ERS Task Force on Primary Ciliary Dyskinesia in Children
Mar 11, 2011·Cytoskeleton·Takahiro KohnoRitsu Kamiya
Apr 19, 2011·American Journal of Human Genetics·Masha MazorRuti Parvari
Jun 22, 2011·Cytoskeleton·Dennis R DienerJoel L Rosenbaum
Nov 9, 2011·The Journal of Cell Biology·Gaia PiginoTakashi Ishikawa
Mar 6, 2012·Nature Genetics·Hannah M MitchisonDavid R Mitchell
Jul 4, 2012·Bioarchitecture·Gaia Pigino, Takashi Ishikawa
Oct 2, 2012·American Journal of Human Genetics·Heike OlbrichHeymut Omran
Oct 9, 2012·American Journal of Human Genetics·Amjad HoraniThomas W Ferkol
Dec 25, 2012·American Journal of Human Genetics·Michael R KnowlesUNKNOWN Genetic Disorders of Mucociliary Clearance Consortium
Dec 25, 2012·American Journal of Human Genetics·Alexandros OnoufriadisHannah M Mitchison
Jun 26, 2013·American Journal of Respiratory and Critical Care Medicine·Michael R KnowlesMargaret W Leigh
Jun 26, 2013·Human Mutation·M Leigh Anne DanielsMaimoona A Zariwala
Jul 16, 2013·American Journal of Human Genetics·Rim HjeijHeymut Omran
Jul 23, 2013·Nature Genetics·Aarti TarkarHeymut Omran
Sep 13, 2013·Annals of the American Thoracic Society·Margaret W LeighMichael R Knowles
Sep 24, 2013·American Journal of Human Genetics·Michael R KnowlesMaimoona A Zariwala
Oct 8, 2013·American Journal of Human Genetics·Christina Austin-TseFriedhelm Hildebrandt
Feb 27, 2014·American Journal of Respiratory and Critical Care Medicine·Michael R KnowlesMaimoona A Zariwala
Sep 5, 2014·The European Respiratory Journal·Johanna RaidtClaudius Werner

❮ Previous
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Citations

Sep 30, 2015·Pediatric Pulmonology·Adam J ShapiroUNKNOWN Genetic Disorders of Mucociliary Clearance Consortium
Jun 16, 2015·American Journal of Human Genetics·Ludovic JeansonMarie Legendre
Nov 8, 2015·Paediatric Respiratory Reviews·Mike John HarrisonMarcus Peter Kennedy
Oct 20, 2015·Paediatric Respiratory Reviews·Amjad HoraniSteven L Brody
Aug 16, 2016·Clinics in Chest Medicine·Michael R KnowlesMargaret Leigh
Feb 26, 2016·American Journal of Respiratory Cell and Molecular Biology·Gerard W DoughertyHeymut Omran
Nov 5, 2016·European Journal of Immunology·Sebastian FuchsStephan Ehl
Dec 15, 2016·Journal of Proteome Research·Matthew W FosterScott M Palmer
Oct 1, 2016·Scientific Reports·Irina SedykhYevgenya Grinblat
Dec 13, 2016·Cold Spring Harbor Perspectives in Biology·Xiaoyan ZhuPinfen Yang
Feb 16, 2017·American Journal of Respiratory and Critical Care Medicine·Amelia ShoemarkClaire Hogg
Aug 3, 2018·Cytoskeleton·Karl F LechtreckKiersten B Hilderhoff
Sep 7, 2018·Journal of Cell Science·Ferheen AbbasiMasahito Ikawa
Apr 10, 2018·BMC Proceedings·Florian HalbeisenJane S Lucas
Jan 18, 2017·European Respiratory Review : an Official Journal of the European Respiratory Society·Nisreen RummanJane S Lucas
Dec 15, 2015·The European Respiratory Journal·Claudius WernerHeymut Omran
Nov 12, 2016·The European Respiratory Journal·Jane S LucasClaudia E Kuehni
Feb 23, 2018·The European Respiratory Journal·Amelia ShoemarkClaire Hogg
Nov 26, 2019·Pediatric Pulmonology·Nagehan EmiralioğluUğur Özçelik
Oct 2, 2019·Translational Science of Rare Diseases·Margaret W LeighMichael R Knowles
Oct 12, 2019·American Journal of Respiratory Cell and Molecular Biology·Susan K Dutcher, Steven L Brody
Sep 24, 2019·American Journal of Respiratory Cell and Molecular Biology·Sandra CindrićHeymut Omran
Feb 16, 2020·The European Respiratory Journal·Amelia ShoemarkUNKNOWN representing the BEAT-PCD Network Guideline Development Group
Apr 14, 2016·Current Opinion in Pediatrics·Carlos E Milla
Aug 29, 2018·Multidisciplinary Respiratory Medicine·Martina ContariniJames D Chalmers
Mar 22, 2019·American Journal of Respiratory Cell and Molecular Biology·Weining YinLawrence E Ostrowski
Jul 27, 2018·Current Allergy and Asthma Reports·Wei-Jie GuanDe Yun Wang
Sep 19, 2020·Nature Reviews. Disease Primers·Julia WallmeierHeymut Omran
Jun 27, 2018·Respiratory Research·Chris O'CallaghanRobert A Hirst
Apr 14, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christine M LuskAnn G Schwartz
Nov 27, 2020·The Journal of Pediatrics·Amjad Horani, Thomas W Ferkol
Dec 16, 2020·Nature Structural & Molecular Biology·Iris Grossman-HahamRonald D Vale

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