Expanding the genetic and clinical spectrum of osteogenesis imperfecta: identification of novel rare pathogenic variants in type I collagen-encoding genes
IntroductionOsteogenesis imperfecta (OI) is a clinically and genetically heterogeneous skeletal disorder. The majority of affected cases are attributed to autosomal dominant pathogenic variants (PVs) found in the COL1A1 and COL1A2 genes, which encode type I collagen. However, PVs in other genes invo...
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| Format: | Article |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1254695/full |
| _version_ | 1828715864106467328 |
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| author | Francesco Paduano Rita Fischetto Biagio Moretti Danila De Vito Marco Tatullo |
| author_facet | Francesco Paduano Rita Fischetto Biagio Moretti Danila De Vito Marco Tatullo |
| author_sort | Francesco Paduano |
| collection | DOAJ |
| description | IntroductionOsteogenesis imperfecta (OI) is a clinically and genetically heterogeneous skeletal disorder. The majority of affected cases are attributed to autosomal dominant pathogenic variants (PVs) found in the COL1A1 and COL1A2 genes, which encode type I collagen. However, PVs in other genes involved in collagen posttranslational modification, processing, crosslinking, osteoblast differentiation, and bone mineralization have also been associated with OI.MethodsIn this study, we present the results of next-generation sequencing (NGS) analysis using a custom panel of 11 genes known to be associated with OI. This clinical study enrolled a total of 10 patients, comprising 7 male and 3 female patients from 7 families, all from the Puglia Region in South Italy, providing a detailed overview of their age, gender, family history, OI type, and non-skeletal features.ResultsThe genetic analysis revealed 5 PVs in the COL1A1 gene and 2 PVs in the COL1A2 gene. Importantly, three of these PVs have not been previously reported in the literature. These include two novel heterozygous frameshift PVs in COL1A1 (c.2890_2893del and c.3887del) and one novel heterozygous missense PV in COL1A2 (c.596G>T).DiscussionThe identification of these previously unreported PVs expands the variant spectrum of the COL1A1 and COL1A2 genes and may have implications for accurate diagnosis, genetic counselling, and potential therapeutic interventions in affected individuals and their families. |
| first_indexed | 2024-03-11T16:58:39Z |
| format | Article |
| id | doaj.art-c7ee3a33740a44caa53e74b26991788d |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-11T16:58:39Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-c7ee3a33740a44caa53e74b26991788d2023-10-20T13:03:52ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-10-011410.3389/fendo.2023.12546951254695Expanding the genetic and clinical spectrum of osteogenesis imperfecta: identification of novel rare pathogenic variants in type I collagen-encoding genesFrancesco Paduano0Rita Fischetto1Biagio Moretti2Danila De Vito3Marco Tatullo4Stem Cells and Medical Genetics Units, Tecnologica Research Institute and Marrelli Health, Crotone, ItalyMetabolic and Genetic Diseases Unit, “Giovanni XXIII” Hospital, Bari, ItalyOrthopaedic and Traumathogic Unit General Hospital Policlinico, Department of Translational Biomedicine and Neuroscience, University “Aldo Moro” of Bari, Bari, ItalyDepartment of Translational Biomedicine and Neuroscience, Medical School, University ”Aldo Moro” of Bari, Bari, ItalyDepartment of Translational Biomedicine and Neuroscience, Medical School, University ”Aldo Moro” of Bari, Bari, ItalyIntroductionOsteogenesis imperfecta (OI) is a clinically and genetically heterogeneous skeletal disorder. The majority of affected cases are attributed to autosomal dominant pathogenic variants (PVs) found in the COL1A1 and COL1A2 genes, which encode type I collagen. However, PVs in other genes involved in collagen posttranslational modification, processing, crosslinking, osteoblast differentiation, and bone mineralization have also been associated with OI.MethodsIn this study, we present the results of next-generation sequencing (NGS) analysis using a custom panel of 11 genes known to be associated with OI. This clinical study enrolled a total of 10 patients, comprising 7 male and 3 female patients from 7 families, all from the Puglia Region in South Italy, providing a detailed overview of their age, gender, family history, OI type, and non-skeletal features.ResultsThe genetic analysis revealed 5 PVs in the COL1A1 gene and 2 PVs in the COL1A2 gene. Importantly, three of these PVs have not been previously reported in the literature. These include two novel heterozygous frameshift PVs in COL1A1 (c.2890_2893del and c.3887del) and one novel heterozygous missense PV in COL1A2 (c.596G>T).DiscussionThe identification of these previously unreported PVs expands the variant spectrum of the COL1A1 and COL1A2 genes and may have implications for accurate diagnosis, genetic counselling, and potential therapeutic interventions in affected individuals and their families.https://www.frontiersin.org/articles/10.3389/fendo.2023.1254695/fullosteogenesis imperfecta (OI)autosomal recessive OInext generation sequencing (NGS)collagen type onemolecular diagnosis of OI |
| spellingShingle | Francesco Paduano Rita Fischetto Biagio Moretti Danila De Vito Marco Tatullo Expanding the genetic and clinical spectrum of osteogenesis imperfecta: identification of novel rare pathogenic variants in type I collagen-encoding genes Frontiers in Endocrinology osteogenesis imperfecta (OI) autosomal recessive OI next generation sequencing (NGS) collagen type one molecular diagnosis of OI |
| title | Expanding the genetic and clinical spectrum of osteogenesis imperfecta: identification of novel rare pathogenic variants in type I collagen-encoding genes |
| title_full | Expanding the genetic and clinical spectrum of osteogenesis imperfecta: identification of novel rare pathogenic variants in type I collagen-encoding genes |
| title_fullStr | Expanding the genetic and clinical spectrum of osteogenesis imperfecta: identification of novel rare pathogenic variants in type I collagen-encoding genes |
| title_full_unstemmed | Expanding the genetic and clinical spectrum of osteogenesis imperfecta: identification of novel rare pathogenic variants in type I collagen-encoding genes |
| title_short | Expanding the genetic and clinical spectrum of osteogenesis imperfecta: identification of novel rare pathogenic variants in type I collagen-encoding genes |
| title_sort | expanding the genetic and clinical spectrum of osteogenesis imperfecta identification of novel rare pathogenic variants in type i collagen encoding genes |
| topic | osteogenesis imperfecta (OI) autosomal recessive OI next generation sequencing (NGS) collagen type one molecular diagnosis of OI |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1254695/full |
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