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Clinical features and molecular characterization of Chinese patients with FKBP10 variants
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10094084/ https://www.ncbi.nlm.nih.gov/pubmed/36655627 http://dx.doi.org/10.1002/mgg3.2122 |
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author | Tan, Zhijia Shek, Hiu Tung Chen, Peikai Dong, Zhongxin Zhou, Yapeng Yin, Shijie Qiu, Anmei Dong, Lina Gao, Bo To, Michael Kai Tsun |
author_facet | Tan, Zhijia Shek, Hiu Tung Chen, Peikai Dong, Zhongxin Zhou, Yapeng Yin, Shijie Qiu, Anmei Dong, Lina Gao, Bo To, Michael Kai Tsun |
author_sort | Tan, Zhijia |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10094084 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100940842023-04-13 Clinical features and molecular characterization of Chinese patients with FKBP10 variants Tan, Zhijia Shek, Hiu Tung Chen, Peikai Dong, Zhongxin Zhou, Yapeng Yin, Shijie Qiu, Anmei Dong, Lina Gao, Bo To, Michael Kai Tsun Mol Genet Genomic Med Original Articles 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. John Wiley and Sons Inc. 2023-01-19 /pmc/articles/PMC10094084/ /pubmed/36655627 http://dx.doi.org/10.1002/mgg3.2122 Text en © 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Tan, Zhijia Shek, Hiu Tung Chen, Peikai Dong, Zhongxin Zhou, Yapeng Yin, Shijie Qiu, Anmei Dong, Lina Gao, Bo To, Michael Kai Tsun Clinical features and molecular characterization of Chinese patients with FKBP10 variants |
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 | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10094084/ https://www.ncbi.nlm.nih.gov/pubmed/36655627 http://dx.doi.org/10.1002/mgg3.2122 |
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