Clinical features and molecular characterization of Chinese patients with FKBP10 variants
Abstract Background Osteogenesis imperfecta (OI) is a group of rare skeletal dysplasia. Long bone deformity and scoliosis are often associated with progressively deforming types of OI. FKBP65 (encoded by FKBP10, OMIM *607063) plays a crucial role in the processing of type I procollagen. Autosomal re...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-04-01
|
| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.2122 |
| _version_ | 1797847908652941312 |
|---|---|
| author | Zhijia Tan Hiu Tung Shek Peikai Chen Zhongxin Dong Yapeng Zhou Shijie Yin Anmei Qiu Lina Dong Bo Gao Michael Kai Tsun To |
| author_facet | Zhijia Tan Hiu Tung Shek Peikai Chen Zhongxin Dong Yapeng Zhou Shijie Yin Anmei Qiu Lina Dong Bo Gao Michael Kai Tsun To |
| author_sort | Zhijia Tan |
| collection | DOAJ |
| description | Abstract Background Osteogenesis imperfecta (OI) is a group of rare skeletal dysplasia. Long bone deformity and scoliosis are often associated with progressively deforming types of OI. FKBP65 (encoded by FKBP10, OMIM *607063) plays a crucial role in the processing of type I procollagen. Autosomal recessive variants in FKBP10 result in type XI osteogenesis imperfecta. Methods Patients diagnosed with OI were recruited for a genetic test. RT‐PCR and Sanger sequencing were applied to confirm the splicing defect in FKBP10 mRNA with the splice‐site variant. The bone structure was characterized by Goldner's trichrome staining. Bioinformatic analyses of bulk RNA sequencing data were performed to examine the effect of the FKBP10 variant on gene expression. Results Here we reported three children from a consanguineous family harboured a homozygous splice‐site variant (c.918‐3C > G) in FKBP10 intron and developed long bone deformity and early onset of scoliosis. We also observed frequent long bone fractures and spinal deformity in another 3 OI patients with different FKBP10 variants. The homozygous splicing variant identified in the fifth intron of FKBP10 (c.918‐3C > G) led to abnormal RNA processing and loss of FKBP65 protein and consequently resulted in aberrant collagen alignment and porous bone morphology. Analysis of transcriptomic data indicated that genes involved in protein processing and osteoblast differentiation were significantly affected in the patient‐derived osteoblasts. Conclusion Our study characterized the clinical features of OI patients with FKBP10 variants and revealed the pathogenesis of the c.918‐3C > G variant. The molecular analyses helped to gain insight into the deleterious effects of FKBP10 variants on collagen processing and osteoblast differentiation. |
| first_indexed | 2024-04-09T18:18:52Z |
| format | Article |
| id | doaj.art-6d2ef864299c4f9a9221c94d5512513e |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-09T18:18:52Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-6d2ef864299c4f9a9221c94d5512513e2023-04-12T15:07:56ZengWileyMolecular Genetics & Genomic Medicine2324-92692023-04-01114n/an/a10.1002/mgg3.2122Clinical features and molecular characterization of Chinese patients with FKBP10 variantsZhijia Tan0Hiu Tung Shek1Peikai Chen2Zhongxin Dong3Yapeng Zhou4Shijie Yin5Anmei Qiu6Lina Dong7Bo Gao8Michael Kai Tsun To9Department of Orthopaedics and Traumatology The University of Hong Kong‐Shenzhen Hospital Shenzhen ChinaDepartment of Orthopaedics and Traumatology The University of Hong Kong‐Shenzhen Hospital Shenzhen ChinaDepartment of Orthopaedics and Traumatology The University of Hong Kong‐Shenzhen Hospital Shenzhen ChinaDepartment of Orthopaedics and Traumatology The University of Hong Kong‐Shenzhen Hospital Shenzhen ChinaDepartment of Orthopaedics and Traumatology The University of Hong Kong‐Shenzhen Hospital Shenzhen ChinaDepartment of Orthopaedics and Traumatology The University of Hong Kong‐Shenzhen Hospital Shenzhen ChinaDepartment of Orthopaedics and Traumatology The University of Hong Kong‐Shenzhen Hospital Shenzhen ChinaDepartment of Orthopaedics and Traumatology The University of Hong Kong‐Shenzhen Hospital Shenzhen ChinaDepartment of Orthopaedics and Traumatology The University of Hong Kong‐Shenzhen Hospital Shenzhen ChinaDepartment of Orthopaedics and Traumatology The University of Hong Kong‐Shenzhen Hospital Shenzhen ChinaAbstract Background Osteogenesis imperfecta (OI) is a group of rare skeletal dysplasia. Long bone deformity and scoliosis are often associated with progressively deforming types of OI. FKBP65 (encoded by FKBP10, OMIM *607063) plays a crucial role in the processing of type I procollagen. Autosomal recessive variants in FKBP10 result in type XI osteogenesis imperfecta. Methods Patients diagnosed with OI were recruited for a genetic test. RT‐PCR and Sanger sequencing were applied to confirm the splicing defect in FKBP10 mRNA with the splice‐site variant. The bone structure was characterized by Goldner's trichrome staining. Bioinformatic analyses of bulk RNA sequencing data were performed to examine the effect of the FKBP10 variant on gene expression. Results Here we reported three children from a consanguineous family harboured a homozygous splice‐site variant (c.918‐3C > G) in FKBP10 intron and developed long bone deformity and early onset of scoliosis. We also observed frequent long bone fractures and spinal deformity in another 3 OI patients with different FKBP10 variants. The homozygous splicing variant identified in the fifth intron of FKBP10 (c.918‐3C > G) led to abnormal RNA processing and loss of FKBP65 protein and consequently resulted in aberrant collagen alignment and porous bone morphology. Analysis of transcriptomic data indicated that genes involved in protein processing and osteoblast differentiation were significantly affected in the patient‐derived osteoblasts. Conclusion Our study characterized the clinical features of OI patients with FKBP10 variants and revealed the pathogenesis of the c.918‐3C > G variant. The molecular analyses helped to gain insight into the deleterious effects of FKBP10 variants on collagen processing and osteoblast differentiation.https://doi.org/10.1002/mgg3.2122FKBP10geneticsosteogenesis imperfecta |
| spellingShingle | Zhijia Tan Hiu Tung Shek Peikai Chen Zhongxin Dong Yapeng Zhou Shijie Yin Anmei Qiu Lina Dong Bo Gao Michael Kai Tsun To Clinical features and molecular characterization of Chinese patients with FKBP10 variants Molecular Genetics & Genomic Medicine FKBP10 genetics osteogenesis imperfecta |
| title | Clinical features and molecular characterization of Chinese patients with FKBP10 variants |
| title_full | Clinical features and molecular characterization of Chinese patients with FKBP10 variants |
| title_fullStr | Clinical features and molecular characterization of Chinese patients with FKBP10 variants |
| title_full_unstemmed | Clinical features and molecular characterization of Chinese patients with FKBP10 variants |
| title_short | Clinical features and molecular characterization of Chinese patients with FKBP10 variants |
| title_sort | clinical features and molecular characterization of chinese patients with fkbp10 variants |
| topic | FKBP10 genetics osteogenesis imperfecta |
| url | https://doi.org/10.1002/mgg3.2122 |
| work_keys_str_mv | AT zhijiatan clinicalfeaturesandmolecularcharacterizationofchinesepatientswithfkbp10variants AT hiutungshek clinicalfeaturesandmolecularcharacterizationofchinesepatientswithfkbp10variants AT peikaichen clinicalfeaturesandmolecularcharacterizationofchinesepatientswithfkbp10variants AT zhongxindong clinicalfeaturesandmolecularcharacterizationofchinesepatientswithfkbp10variants AT yapengzhou clinicalfeaturesandmolecularcharacterizationofchinesepatientswithfkbp10variants AT shijieyin clinicalfeaturesandmolecularcharacterizationofchinesepatientswithfkbp10variants AT anmeiqiu clinicalfeaturesandmolecularcharacterizationofchinesepatientswithfkbp10variants AT linadong clinicalfeaturesandmolecularcharacterizationofchinesepatientswithfkbp10variants AT bogao clinicalfeaturesandmolecularcharacterizationofchinesepatientswithfkbp10variants AT michaelkaitsunto clinicalfeaturesandmolecularcharacterizationofchinesepatientswithfkbp10variants |