Investigation of a family affected by early-onset osteoarthritis – proposal of a clinical pathway and bioinformatics pipeline for the investigation of cases of familial OA
Abstract Background Familial cases of early-onset osteoarthritis (OA) are rare although the exact prevalence is unknown. Early recognition of underlying OA-associated disorders is vital for targeted treatment, when available, and genetic counselling, in case of skeletal dysplasias. Currently, there...
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | BMC Musculoskeletal Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12891-023-06691-5 |
| _version_ | 1797779101695606784 |
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| author | Leticia A. Deveza Andreas Zankl David J. Hunter |
| author_facet | Leticia A. Deveza Andreas Zankl David J. Hunter |
| author_sort | Leticia A. Deveza |
| collection | DOAJ |
| description | Abstract Background Familial cases of early-onset osteoarthritis (OA) are rare although the exact prevalence is unknown. Early recognition of underlying OA-associated disorders is vital for targeted treatment, when available, and genetic counselling, in case of skeletal dysplasias. Currently, there is no clear guidance on how best to investigate families affected by early-onset OA. Methods We investigated a family with multiple members affected by early-onset OA (age at onset ≤ 40 years). Clinical and demographic characteristics were collected, followed by laboratory investigations screening for a range of potential OA-associated disorders, and whole genome sequencing in selected individuals. Results Seventeen members of the family were included (7 affected and 10 non-affected). There was an even split between the two sexes and two participants were under 18 years old. No pattern of abnormality was seen in the laboratory investigation that could explain the OA phenotype in the family. Whole-genome sequencing was perfomed in one participant and analysed for likely pathogenic variants in genes known to be associated with skeletal dysplasias. A heterozygous variant in the COL2A1 gene was identified (p.Arg519Cys). Confirmatory tests were performed in five additional participants (four affected and one unaffected). Conclusion The methodology used in this study, including the clinical pathway and bioinformatics pipeline, could be applied to other families affected by early-onset OA. |
| first_indexed | 2024-03-12T23:26:53Z |
| format | Article |
| id | doaj.art-27d993dfe43a4b9082111e480a09eb9c |
| institution | Directory Open Access Journal |
| issn | 1471-2474 |
| language | English |
| last_indexed | 2024-03-12T23:26:53Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Musculoskeletal Disorders |
| spelling | doaj.art-27d993dfe43a4b9082111e480a09eb9c2023-07-16T11:03:44ZengBMCBMC Musculoskeletal Disorders1471-24742023-07-012411810.1186/s12891-023-06691-5Investigation of a family affected by early-onset osteoarthritis – proposal of a clinical pathway and bioinformatics pipeline for the investigation of cases of familial OALeticia A. Deveza0Andreas Zankl1David J. Hunter2Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine, University of SydneySydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine, University of SydneySydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine, University of SydneyAbstract Background Familial cases of early-onset osteoarthritis (OA) are rare although the exact prevalence is unknown. Early recognition of underlying OA-associated disorders is vital for targeted treatment, when available, and genetic counselling, in case of skeletal dysplasias. Currently, there is no clear guidance on how best to investigate families affected by early-onset OA. Methods We investigated a family with multiple members affected by early-onset OA (age at onset ≤ 40 years). Clinical and demographic characteristics were collected, followed by laboratory investigations screening for a range of potential OA-associated disorders, and whole genome sequencing in selected individuals. Results Seventeen members of the family were included (7 affected and 10 non-affected). There was an even split between the two sexes and two participants were under 18 years old. No pattern of abnormality was seen in the laboratory investigation that could explain the OA phenotype in the family. Whole-genome sequencing was perfomed in one participant and analysed for likely pathogenic variants in genes known to be associated with skeletal dysplasias. A heterozygous variant in the COL2A1 gene was identified (p.Arg519Cys). Confirmatory tests were performed in five additional participants (four affected and one unaffected). Conclusion The methodology used in this study, including the clinical pathway and bioinformatics pipeline, could be applied to other families affected by early-onset OA.https://doi.org/10.1186/s12891-023-06691-5OsteoarthritisDysplasiaArthritis |
| spellingShingle | Leticia A. Deveza Andreas Zankl David J. Hunter Investigation of a family affected by early-onset osteoarthritis – proposal of a clinical pathway and bioinformatics pipeline for the investigation of cases of familial OA BMC Musculoskeletal Disorders Osteoarthritis Dysplasia Arthritis |
| title | Investigation of a family affected by early-onset osteoarthritis – proposal of a clinical pathway and bioinformatics pipeline for the investigation of cases of familial OA |
| title_full | Investigation of a family affected by early-onset osteoarthritis – proposal of a clinical pathway and bioinformatics pipeline for the investigation of cases of familial OA |
| title_fullStr | Investigation of a family affected by early-onset osteoarthritis – proposal of a clinical pathway and bioinformatics pipeline for the investigation of cases of familial OA |
| title_full_unstemmed | Investigation of a family affected by early-onset osteoarthritis – proposal of a clinical pathway and bioinformatics pipeline for the investigation of cases of familial OA |
| title_short | Investigation of a family affected by early-onset osteoarthritis – proposal of a clinical pathway and bioinformatics pipeline for the investigation of cases of familial OA |
| title_sort | investigation of a family affected by early onset osteoarthritis proposal of a clinical pathway and bioinformatics pipeline for the investigation of cases of familial oa |
| topic | Osteoarthritis Dysplasia Arthritis |
| url | https://doi.org/10.1186/s12891-023-06691-5 |
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