Valentin Ruault1, Kevin Yauy2, Aurélie Fabre1, Mélanie Fradin3, Julien Van-Gils4, Chloé Angelini4, Geneviève Baujat5, Patricia Blanchet1, Silvestre Cuinat6, Bertrand Isidor6, Christian Jorgensen7, Didier Lacombe4, Sébastien Moutton8, Sylvie Odent3, Elodie Sanchez9, Sabine Sigaudy10, Isabelle Touitou9, Marjolaine Willems1, Florence Apparailly9, David Geneviève9, Mouna Barat-Houari1. 1. Université de Montpellier, Centre Hospitalier Universitaire Montpellier, CLAD Sud Languedoc-Roussillon, Montpellier, France. 2. Université de Montpellier, Centre Hospitalier Universitaire Montpellier, CLAD Sud Languedoc-Roussillon and SeqOne, Montpellier, France, and Institute of Advanced Biosciences, Université Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Grenoble, France. 3. Centre Hospitalier Universitaire Hôpital Sud, CLAD Ouest, CNRS UMR 6290, Université de Rennes, Rennes, France. 4. Hôpital Pellegrin, CLAD Sud-Ouest, Bordeaux, France. 5. Hôpital Necker-Enfants Malades, Paris, France. 6. Centre Hospitalier Universitaire Nantes, CLAD Ouest, Nantes, France. 7. Université de Montpellier, Centre Hospitalier Universitaire Montpellier, INSERM, Montpellier, France. 8. Centre Pluridisciplinaire de Diagnostic Prénatal, Pôle Mère-Enfant, Maison de Santé Protestante de Bordeaux-Bagatelle, Talence, France. 9. Université de Montpellier, Centre Hospitalier Universitaire Montpellier, CLAD Sud Languedoc-Roussillon, INSERM, Montpellier, France. 10. Centre Hospitalier Universitaire de Marseille, Hôpital de la Timone, Marseille, France.
Abstract
OBJECTIVE: Osteoarthritis (OA) is the most common joint disease worldwide. The etiology of OA is varied, ranging from multifactorial to environmental to monogenic. In a condition called early-onset OA, OA occurs at an earlier age than is typical in the general population. To our knowledge, there have been no large-scale genetic studies of individuals with early-onset OA. The present study was undertaken to investigate causes of monogenic OA in individuals with nonsyndromic early-onset OA. METHODS: The study probands were 45 patients with nonsyndromic early-onset OA who were referred to our skeletal disease center by skeletal dysplasia experts between 2013 and 2019. Criteria for early-onset OA included radiographic evidence, body mass index ≤30 kg/m2 , age at onset ≤50 years, and involvement of ≥1 joint site. Molecular analysis was performed with a next-generation sequencing panel. RESULTS: We identified a genetic variant in 13 probands (29%); the affected gene was COL2A1 in 11, ACAN in 1, and SLC26A2 in 1. After familial segregation analysis, 20 additional individuals were identified. The mean ± SD age at onset of joint pain was 19.5 ± 3.9 years (95% confidence interval 3-47). Eighteen of 33 subjects (55%) with nonsyndromic early-onset OA and a genetic variant had had at least 1 joint replacement (mean ± SD age at first joint replacement 41 ± 4.2 years; mean number of joint replacements 2.6 per individual), and 21 (45%) of the joint replacement surgeries were performed when the patient was <45 years old. Of the 20 patients age >40 years, 17 (85%) had had at least 1 joint replacement. CONCLUSION: We confirmed that COL2A1 is the main monogenic cause of nonsyndromic early-onset OA. However, on the basis of genetic heterogeneity of early-onset OA, we recommend next-generation sequencing for all individuals who undergo joint replacement prior to the age of 45 years. Lifestyle recommendations for prevention should be implemented.
OBJECTIVE:Osteoarthritis (OA) is the most common joint disease worldwide. The etiology of OA is varied, ranging from multifactorial to environmental to monogenic. In a condition called early-onset OA, OA occurs at an earlier age than is typical in the general population. To our knowledge, there have been no large-scale genetic studies of individuals with early-onset OA. The present study was undertaken to investigate causes of monogenic OA in individuals with nonsyndromic early-onset OA. METHODS: The study probands were 45 patients with nonsyndromic early-onset OA who were referred to our skeletal disease center by skeletal dysplasia experts between 2013 and 2019. Criteria for early-onset OA included radiographic evidence, body mass index ≤30 kg/m2 , age at onset ≤50 years, and involvement of ≥1 joint site. Molecular analysis was performed with a next-generation sequencing panel. RESULTS: We identified a genetic variant in 13 probands (29%); the affected gene was COL2A1 in 11, ACAN in 1, and SLC26A2 in 1. After familial segregation analysis, 20 additional individuals were identified. The mean ± SD age at onset of joint pain was 19.5 ± 3.9 years (95% confidence interval 3-47). Eighteen of 33 subjects (55%) with nonsyndromic early-onset OA and a genetic variant had had at least 1 joint replacement (mean ± SD age at first joint replacement 41 ± 4.2 years; mean number of joint replacements 2.6 per individual), and 21 (45%) of the joint replacement surgeries were performed when the patient was <45 years old. Of the 20 patients age >40 years, 17 (85%) had had at least 1 joint replacement. CONCLUSION: We confirmed that COL2A1 is the main monogenic cause of nonsyndromic early-onset OA. However, on the basis of genetic heterogeneity of early-onset OA, we recommend next-generation sequencing for all individuals who undergo joint replacement prior to the age of 45 years. Lifestyle recommendations for prevention should be implemented.
Authors: Michael J Jurynec; Catherine M Gavile; Matthew Honeggar; Ying Ma; Shivakumar R Veerabhadraiah; Kendra A Novak; Kazuyuki Hoshijima; Nikolas H Kazmers; David J Grunwald Journal: Ann Rheum Dis Date: 2022-06-22 Impact factor: 27.973
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Authors: Till Joscha Demal; Tasja Scholz; Maja Hempel; Georg Rosenberger; Helke Schüler; Jakob Olfe; Anja Fröhlich; Fabian Speth; Yskert von Kodolitsch; Thomas S Mir; Hermann Reichenspurner; Christian Kubisch Journal: Sci Rep Date: 2022-03-16 Impact factor: 4.379