Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia |
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| Authors: | Vinod Dasa James R.B. Eastwood Michal Podgorski Heewon Park Christopher Blackstock Tetyana Antoshchenko Piotr Rogala Tadeusz Bieganski S. Michal Jazwinski Malwina Czarny‐Ratajczak |
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| Affiliation: | 1. Department of Orthopaedic Surgery, Louisiana State University Health Sciences Center, New Orleans, Louisiana;2. Tulane Center for Aging, Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana;3. Department of Diagnostic Imaging, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland;4. Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, Louisiana;5. Department of Spine Surgery, Oncological Orthopedics and Traumatology, W. Dega University Hospital, Poznan University of Medical Sciences, Poznan, Poland;6. Department of Physiotherapy, H. Cegielski State College, Gniezno, Poland;7. https://orcid.org/0000-0002-5601-7253;8. Malwina Czarny‐Ratajczak, Tulane Center for Aging, Department of Medicine, Tulane University School of Medicine, New Orleans, LA. |
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| Abstract: | Mutations in the COMP, COL9A1, COL9A2, COL9A3, MATN3, and SLC26A2 genes cause approximately 70% of multiple epiphyseal dysplasia (MED) cases. The genetic changes involved in the etiology of the remaining cases are still unknown, suggesting that other genes contribute to MED development. Our goal was to identify a mutation causing an autosomal dominant form of MED in a large multigenerational family. Initially, we excluded all genes known to be associated with autosomal dominant MED by using microsatellite and SNP markers. Follow‐up with whole‐exome sequencing analysis revealed a mutation c.2032G>A (p.Gly678Arg) in the COL2A1 gene (NCBI Reference Sequence: NM_001844.4), which co‐segregated with the disease phenotype in this family, manifested by severe hip dysplasia and osteoarthritis. One of the affected family members had a double‐layered patella, which is frequently seen in patients with autosomal recessive MED caused by DTDST mutations and sporadically in the dominant form of MED caused by COL9A2 defect. |
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| Keywords: | double‐layered patella multiple epiphyseal dysplasia novel mutation in COL2A1 |
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