The international registry for primary ciliary dyskinesia reveals regional variation of genotypes and significant genotype-phenotype correlations

<bold>Introduction:</bold> Primary ciliary dyskinesia (PCD, ORPHA:244) is a rare, clinically and genetically heterogeneous group of diseases characterised by deficient mucociliary clearance of the airways. <bold>Aims and objectives:</bold> Our aim was to characterize the underlying genetic defects, assess the geographic distribution and investigate the global impact of genotypes on clinical aspects of the disease, focusing on lung function and laterality defects. <bold>Methods:</bold> Using the International PCD registry, genetic and clinical data were collected from 19 countries (Europe (15), Asia (2), South America (2)) participating in the ERN LUNG PCD Core. Genetic variants were evaluated (ACMG) and the regional distribution was assessed. The association between genotypes and laterality defects and FEV1 z-scores was analysed. <bold>Results:</bold> We found disease-causing variants in 46 PCD genes in 89% (n=1,236) of the individuals, with clear regional differences between countries, mainly due to founder effects. The prevalence of laterality defects in the cohort was 42%. The prevalence of PCD genotypes associated with laterality defects varied widely between countries (28-69%). PCD individuals had impaired FEV1 z-scores, which were significantly lower for CCDC39, CCDC40, CCNO and less severely reduced for DNAH11 and ODAD1. <bold>Conclusion:</bold> This multinational dataset of genetic variants and their distribution provides insights into the genetic epidemiology of PCD and the phenotypic characteristics such as the course of lung function. Several participating centres are Health Care Providers in the ERN LUNG PCD Core and/or members of BEAT-PCD clinical research collaboration (CRC) supported by the ERS.

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Published
2024-09-14
DOI
https://doi.org/10.1183/13993003.congress-2024.oa2789
Primary Topic
Cystic Fibrosis Research Advances
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article
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article

The international registry for primary ciliary dyskinesia reveals regional variation of genotypes and significant genotype-phenotype correlations

June K. Marthin, Heymut Omran, Sebastian F. N. Bode, Rodrigo Abensur Athanazio et al.
Cystic Fibrosis Research Advances
article

The international registry for primary ciliary dyskinesia reveals regional variation of genotypes and significant genotype-phenotype correlations

June K. Marthin, Heymut Omran, Sebastian F. N. Bode, Rodrigo Abensur Athanazio, Debora Maj, Claire Hogg, Hannah M. Mitchison, Melissa Borrelli, Michael R. Loebinger, Panayiotis Κouis, Eitan Kerem, Andrzej Pogorzelski, Sarah Riepenhausen, O. Baron, Eleonora Dehlink, Nicola Ullmann, C.R. Hansen, Ben O. Staar, Juan E. Balinotti, Nagehan Emiralioğlu, Panayiotis Yiallouros, Sandra Rovira‐Amigo, Rossella Fonnesu, Israel Amirav, Sivagurunathan Sutharsan, Jobst Roehmel, Sandra Diepenhorst, Robert Walter Körner, Kim G. Nielsen, Tabea Nöthe-Menchen, Heike Olbrich, Felix C. Ringshausen, Jane S. Lucas, S.B. Carr, Anne Schlegtendal, Mathias Geldermann Holgersen, Marcus Alexander Mall, Serena Gracci, Nisreen Rumman, Martin Wetzke, Peter Ďurdík, Natalie Lorent, Petra Pennekamp, Synne Sperstad Kennelly, Micha Aviram, Ela Erdem Eralp, Mieke Boon, Amelia Shoemark, Henryk Mazurek, Sandra von Hardenberg, Jörg Große-Onnebrink, Karsten Kötz, Suzanne Crowley, Ewa Ziętkiewicz, Eric G. Haarman, Johanna Raidt, Massimo Pifferi, Uğur Özçelik, Vendula Martinů, Karolina Gwozdziewicz, Simon Thomas, Bernd Dworniczak, Michał Witt, Woolf T. Walker, Varghese Julian
article en

Abstract

<bold>Introduction:</bold> Primary ciliary dyskinesia (PCD, ORPHA:244) is a rare, clinically and genetically heterogeneous group of diseases characterised by deficient mucociliary clearance of the airways. <bold>Aims and objectives:</bold> Our aim was to characterize the underlying genetic defects, assess the geographic distribution and investigate the global impact of genotypes on clinical aspects of the disease, focusing on lung function and laterality defects. <bold>Methods:</bold> Using the International PCD registry, genetic and clinical data were collected from 19 countries (Europe (15), Asia (2), South America (2)) participating in the ERN LUNG PCD Core. Genetic variants were evaluated (ACMG) and the regional distribution was assessed. The association between genotypes and laterality defects and FEV1 z-scores was analysed. <bold>Results:</bold> We found disease-causing variants in 46 PCD genes in 89% (n=1,236) of the individuals, with clear regional differences between countries, mainly due to founder effects. The prevalence of laterality defects in the cohort was 42%. The prevalence of PCD genotypes associated with laterality defects varied widely between countries (28-69%). PCD individuals had impaired FEV1 z-scores, which were significantly lower for CCDC39, CCDC40, CCNO and less severely reduced for DNAH11 and ODAD1. <bold>Conclusion:</bold> This multinational dataset of genetic variants and their distribution provides insights into the genetic epidemiology of PCD and the phenotypic characteristics such as the course of lung function. Several participating centres are Health Care Providers in the ERN LUNG PCD Core and/or members of BEAT-PCD clinical research collaboration (CRC) supported by the ERS.

University of Pisa (IT), Oslo University Hospital (NO), Tel Aviv University (IL), University of Nicosia (CY), Lund University (SE), Al-Quds University (PS), Charles University (CZ), University of Münster (DE), Hadassah Medical Center (IL), Great Ormond Street Hospital (GB), Soroka Medical Center (IL), Sahlgrenska University Hospital (SE), Copenhagen University Hospital (DK), Rigshospitalet (DK), Harefield Hospital (GB), University Hospital Southampton NHS Foundation Trust (GB), University of Cyprus (CY), Medizinische Hochschule Hannover (DE), Humboldt-Universität zu Berlin (DE), Ruhrlandklinik (DE), Emma Kinderziekenhuis (NL), Royal Brompton Hospital (GB), University Hospital in Motol (CZ), Augenstern (DE), Drottning Silvias barn- och ungdomssjukhus (SE), University Hospital Münster (DE), Cystic Fibrosis Research Foundation (IT), Schneider Children's Medical Center (IL), Federico II University Hospital (IT), Institute of Human Genetics (PL), National Center for Tuberculosis and Lung Disease (GE), Bambino Gesù Children's Hospital (IT), Vall d'Hebron Hospital Universitari (ES), Archbishop Makarios III Hospital (CY), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR), Institute of Plant Genetics, Polish Academy of Sciences (PL), Amsterdam University Medical Centers (NL), Katholisches Klinikum Bochum (DE), University Hospital Cologne (DE), University Hospital Ulm (DE), Azienda Ospedaliera Universitaria Pisana (IT), Hospital General de Niños Ricardo Gutierrez (AR), University College London (GB), Hacettepe University (TR), Comenius University Bratislava (SK), Marmara University (TR), Medical University of Vienna (AT), Salisbury NHS Foundation Trust (GB), University of Gothenburg (SE), KU Leuven (BE)
Openalex Percentile: Top 63%
Cystic Fibrosis Research Advances
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