Diagnostic Challenge of Phenotypic Variability in COL2A1-related Disorders: Four Novel Variants That Expand the Clinical Spectrum
Objective: Heterozygous COL2A1 gene mutations are associated with type 2 collagenopathies, characterized by a wide, diverse, and overlapping clinical spectrum in related diseases. Our goal is to describe the clinical, radiological, and molecular findings of patients with COL2A1-related dysplasia and...
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| Format: | Article |
| Language: | English |
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Galenos Yayincilik
2025-09-01
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| Series: | JCRPE |
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| Online Access: | https://www.jcrpe.org/articles/diagnostic-challenge-of-phenotypic-variability-in-lessemgreatercol2a1lessemgreater-related-disorders-four-novel-variants-that-expand-the-clinical-spectrum/doi/jcrpe.galenos.2025.2024-9-7 |
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| author | Burcu Yeter Yasemin Kendir Demirkol Metin Eser Ahmet Hamdi Akgülle Betül Sözeri Heves Kırmızıbekmez |
| author_facet | Burcu Yeter Yasemin Kendir Demirkol Metin Eser Ahmet Hamdi Akgülle Betül Sözeri Heves Kırmızıbekmez |
| author_sort | Burcu Yeter |
| collection | DOAJ |
| description | Objective: Heterozygous COL2A1 gene mutations are associated with type 2 collagenopathies, characterized by a wide, diverse, and overlapping clinical spectrum in related diseases. Our goal is to describe the clinical, radiological, and molecular findings of patients with COL2A1-related dysplasia and investigate the phenotype-genotype correlation. We also highlight the challenge of categorizing COL2A1-related diseases with similar clinical and radiological phenotypes.
Methods: Six patients from five unrelated families presented with disproportionate short stature.delayed motor milestones, waddling gait, normal intelligence, and similar radiological features, including delayed epiphyseal ossification, epimetaphyseal changes, scoliosis, lordosis, and platyspondyly. All underwent whole exome sequencing. Demographic, clinical, laboratory, and radiological data were retrospectively obtained from hospital records. Segregation analysis was conducted using Sanger sequencing in all patients.
Results: Based on clinical, radiological, and molecular results, the six patients were categorized into kniest dysplasia, spondyloepiphyseal dysplasia congenita, and spondyloepimetaphyseal dysplasia Strudwick type. Four novel variants (c.1023+2T>C, p.Gly465Asp, p.Gly855Asp, p.Gly669Ala) were identified in the COL2A1 gene.
Conclusion: Accurate classification of type 2 collagenopathies is vital to provide appropriate genetic counseling. Predicting extraskeletal manifestations and reducing morbidity through early diagnosis and treatment will significantly improve the quality of life for patients. |
| format | Article |
| id | doaj-art-9c1ddba011cc4d7795890ef57622fda1 |
| institution | Kabale University |
| issn | 1308-5727 1308-5735 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Galenos Yayincilik |
| record_format | Article |
| series | JCRPE |
| spelling | doaj-art-9c1ddba011cc4d7795890ef57622fda12025-08-25T06:26:47ZengGalenos YayincilikJCRPE1308-57271308-57352025-09-0117329730610.4274/jcrpe.galenos.2025.2024-9-7Diagnostic Challenge of Phenotypic Variability in COL2A1-related Disorders: Four Novel Variants That Expand the Clinical SpectrumBurcu Yeter0https://orcid.org/0000-0002-6255-1057Yasemin Kendir Demirkol1https://orcid.org/0000-0001-8016-5224Metin Eser2https://orcid.org/0000-0001-7118-7958Ahmet Hamdi Akgülle3https://orcid.org/0000-0002-1216-9589Betül Sözeri4https://orcid.org/0000-0002-5079-5644Heves Kırmızıbekmez5https://orcid.org/0000-0002-8663-3452University of Health Sciences Türkiye, Ümraniye Training and Research Hospital, Clinic of Pediatric Genetics, İstanbul, TürkiyeUniversity of Health Sciences Türkiye, Ümraniye Training and Research Hospital, Clinic of Pediatric Genetics, İstanbul, TürkiyeUniversity of Health Sciences Türkiye, Ümraniye Training and Research Hospital, Clinic of Medical Genetics, İstanbul, TürkiyeMarmara University Faculty of Medicine, Department of Orthopaedics Surgery and Traumatology, İstanbul, TürkiyeUniversity of Health Sciences Türkiye, Ümraniye Training and Research Hospital, Clinic of Pediatric Rheumatology, İstanbul, TürkiyeUniversity of Health Sciences Türkiye, Ümraniye Training and Research Hospital,Clinic of Pediatric Endocrinology, İstanbul, TürkiyeObjective: Heterozygous COL2A1 gene mutations are associated with type 2 collagenopathies, characterized by a wide, diverse, and overlapping clinical spectrum in related diseases. Our goal is to describe the clinical, radiological, and molecular findings of patients with COL2A1-related dysplasia and investigate the phenotype-genotype correlation. We also highlight the challenge of categorizing COL2A1-related diseases with similar clinical and radiological phenotypes. Methods: Six patients from five unrelated families presented with disproportionate short stature.delayed motor milestones, waddling gait, normal intelligence, and similar radiological features, including delayed epiphyseal ossification, epimetaphyseal changes, scoliosis, lordosis, and platyspondyly. All underwent whole exome sequencing. Demographic, clinical, laboratory, and radiological data were retrospectively obtained from hospital records. Segregation analysis was conducted using Sanger sequencing in all patients. Results: Based on clinical, radiological, and molecular results, the six patients were categorized into kniest dysplasia, spondyloepiphyseal dysplasia congenita, and spondyloepimetaphyseal dysplasia Strudwick type. Four novel variants (c.1023+2T>C, p.Gly465Asp, p.Gly855Asp, p.Gly669Ala) were identified in the COL2A1 gene. Conclusion: Accurate classification of type 2 collagenopathies is vital to provide appropriate genetic counseling. Predicting extraskeletal manifestations and reducing morbidity through early diagnosis and treatment will significantly improve the quality of life for patients.https://www.jcrpe.org/articles/diagnostic-challenge-of-phenotypic-variability-in-lessemgreatercol2a1lessemgreater-related-disorders-four-novel-variants-that-expand-the-clinical-spectrum/doi/jcrpe.galenos.2025.2024-9-7col2a1 genecol2a1-related disordersshort-trunk dwarfismtype 2 collagenopathieswhole exome sequencing |
| spellingShingle | Burcu Yeter Yasemin Kendir Demirkol Metin Eser Ahmet Hamdi Akgülle Betül Sözeri Heves Kırmızıbekmez Diagnostic Challenge of Phenotypic Variability in COL2A1-related Disorders: Four Novel Variants That Expand the Clinical Spectrum JCRPE col2a1 gene col2a1-related disorders short-trunk dwarfism type 2 collagenopathies whole exome sequencing |
| title | Diagnostic Challenge of Phenotypic Variability in COL2A1-related Disorders: Four Novel Variants That Expand the Clinical Spectrum |
| title_full | Diagnostic Challenge of Phenotypic Variability in COL2A1-related Disorders: Four Novel Variants That Expand the Clinical Spectrum |
| title_fullStr | Diagnostic Challenge of Phenotypic Variability in COL2A1-related Disorders: Four Novel Variants That Expand the Clinical Spectrum |
| title_full_unstemmed | Diagnostic Challenge of Phenotypic Variability in COL2A1-related Disorders: Four Novel Variants That Expand the Clinical Spectrum |
| title_short | Diagnostic Challenge of Phenotypic Variability in COL2A1-related Disorders: Four Novel Variants That Expand the Clinical Spectrum |
| title_sort | diagnostic challenge of phenotypic variability in col2a1 related disorders four novel variants that expand the clinical spectrum |
| topic | col2a1 gene col2a1-related disorders short-trunk dwarfism type 2 collagenopathies whole exome sequencing |
| url | https://www.jcrpe.org/articles/diagnostic-challenge-of-phenotypic-variability-in-lessemgreatercol2a1lessemgreater-related-disorders-four-novel-variants-that-expand-the-clinical-spectrum/doi/jcrpe.galenos.2025.2024-9-7 |
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