Lessons learned from a muscle study in nail-patella syndrome
Abstract Background Nail-patella (NPS) syndrome is an autosomal dominant disorder caused by mutations in the LMX1B gene and manifests with involvement of kidneys, nails, eyes as well as skeletal musculature. NPS shows some clinical similarities with Emery-Dreifuss muscular dystrophy. However, thus f...
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BMC
2025-07-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03911-0 |
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| author | Luisa Paul Anne Schänzer Christel Depienne Andreas Hentschel Nicolai Kohlschmidt Ulrike Schara-Schmidt Christopher Jannik Nelke Andreas Roos Heike Kölbel |
| author_facet | Luisa Paul Anne Schänzer Christel Depienne Andreas Hentschel Nicolai Kohlschmidt Ulrike Schara-Schmidt Christopher Jannik Nelke Andreas Roos Heike Kölbel |
| author_sort | Luisa Paul |
| collection | DOAJ |
| description | Abstract Background Nail-patella (NPS) syndrome is an autosomal dominant disorder caused by mutations in the LMX1B gene and manifests with involvement of kidneys, nails, eyes as well as skeletal musculature. NPS shows some clinical similarities with Emery-Dreifuss muscular dystrophy. However, thus far human muscle tissue has not been analysed in the context of NPS to precisely clarify the muscular involvement in this multi-systemic disease. Methods To study the effects of a missense variant in LMX1B on human skeletal muscle, histological, immunofluorescence and ultra-structural studies were performed on a deltoid muscle biopsy performed at the age of 2 aiming to analyse potential pathologies in muscle fibres in addition to unbiased proteomic profiling to identify dysregulated proteins. Results Microscopic work-up of the muscle biopsy revealed no striking pathologies, except for some atrophic fibres. The proteomic analyses unveiled a clustered number of dysregulated keratin proteins among the downregulated proteins. Conclusion Although NPS can also present with a muscular phenotype indicated by muscular weakness of the upper extremities, elevated CK levels and contractures of the elbow joint, there is no evidence of primary muscular involvement due to expression of mutant LMX1B. The examination of human skeletal muscle tissue confirmed the findings from the animal models showing that the skeletal muscle symptoms of NPS may be the result of a developmental disorder of the extremities that leads to impaired muscle mobilisation. |
| format | Article |
| id | doaj-art-bc5e33166de046dc8b208bf0d50085a9 |
| institution | DOAJ |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-bc5e33166de046dc8b208bf0d50085a92025-08-20T03:06:05ZengBMCOrphanet Journal of Rare Diseases1750-11722025-07-0120111010.1186/s13023-025-03911-0Lessons learned from a muscle study in nail-patella syndromeLuisa Paul0Anne Schänzer1Christel Depienne2Andreas Hentschel3Nicolai Kohlschmidt4Ulrike Schara-Schmidt5Christopher Jannik Nelke6Andreas Roos7Heike Kölbel8Department of Pediatric Neurology, Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, University Hospital EssenInstitute of Neuropathology, Justus-Liebig-University GiessenInstitute of Human Genetics, University Hospital Essen, University Duisburg-EssenLeibniz Institute für Analytische Wissenschaften – ISAS – e.V.Institute of Clinical Genetics and Tumour GeneticsDepartment of Pediatric Neurology, Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, University Hospital EssenInstitute of Neurology, University Hospital Düsseldorf, Heinrich Heine University DüsseldorfDepartment of Pediatric Neurology, Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, University Hospital EssenDepartment of Pediatric Neurology, Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, University Hospital EssenAbstract Background Nail-patella (NPS) syndrome is an autosomal dominant disorder caused by mutations in the LMX1B gene and manifests with involvement of kidneys, nails, eyes as well as skeletal musculature. NPS shows some clinical similarities with Emery-Dreifuss muscular dystrophy. However, thus far human muscle tissue has not been analysed in the context of NPS to precisely clarify the muscular involvement in this multi-systemic disease. Methods To study the effects of a missense variant in LMX1B on human skeletal muscle, histological, immunofluorescence and ultra-structural studies were performed on a deltoid muscle biopsy performed at the age of 2 aiming to analyse potential pathologies in muscle fibres in addition to unbiased proteomic profiling to identify dysregulated proteins. Results Microscopic work-up of the muscle biopsy revealed no striking pathologies, except for some atrophic fibres. The proteomic analyses unveiled a clustered number of dysregulated keratin proteins among the downregulated proteins. Conclusion Although NPS can also present with a muscular phenotype indicated by muscular weakness of the upper extremities, elevated CK levels and contractures of the elbow joint, there is no evidence of primary muscular involvement due to expression of mutant LMX1B. The examination of human skeletal muscle tissue confirmed the findings from the animal models showing that the skeletal muscle symptoms of NPS may be the result of a developmental disorder of the extremities that leads to impaired muscle mobilisation.https://doi.org/10.1186/s13023-025-03911-0Nail-patella syndromeElbow contracturesEmery dreyfuss muscle dystrophyLMX1BMuscle proteomics |
| spellingShingle | Luisa Paul Anne Schänzer Christel Depienne Andreas Hentschel Nicolai Kohlschmidt Ulrike Schara-Schmidt Christopher Jannik Nelke Andreas Roos Heike Kölbel Lessons learned from a muscle study in nail-patella syndrome Orphanet Journal of Rare Diseases Nail-patella syndrome Elbow contractures Emery dreyfuss muscle dystrophy LMX1B Muscle proteomics |
| title | Lessons learned from a muscle study in nail-patella syndrome |
| title_full | Lessons learned from a muscle study in nail-patella syndrome |
| title_fullStr | Lessons learned from a muscle study in nail-patella syndrome |
| title_full_unstemmed | Lessons learned from a muscle study in nail-patella syndrome |
| title_short | Lessons learned from a muscle study in nail-patella syndrome |
| title_sort | lessons learned from a muscle study in nail patella syndrome |
| topic | Nail-patella syndrome Elbow contractures Emery dreyfuss muscle dystrophy LMX1B Muscle proteomics |
| url | https://doi.org/10.1186/s13023-025-03911-0 |
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