A De Novo Mutation in <i>COL1A1</i> in a Holstein Calf with Osteogenesis Imperfecta Type II
Osteogenesis imperfecta (OI) type II is a genetic connective tissue disorder characterized by bone fragility, severe skeletal deformities and shortened limbs. OI usually causes perinatal death of affected individuals. OI type II diagnosis in humans is established by the identification of heterozygou...
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MDPI AG
2021-02-01
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| Series: | Animals |
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| author | Joana G. P. Jacinto Irene M. Häfliger Fintan J. McEvoy Cord Drögemüller Jørgen S. Agerholm |
| author_facet | Joana G. P. Jacinto Irene M. Häfliger Fintan J. McEvoy Cord Drögemüller Jørgen S. Agerholm |
| author_sort | Joana G. P. Jacinto |
| collection | DOAJ |
| description | Osteogenesis imperfecta (OI) type II is a genetic connective tissue disorder characterized by bone fragility, severe skeletal deformities and shortened limbs. OI usually causes perinatal death of affected individuals. OI type II diagnosis in humans is established by the identification of heterozygous mutations in genes coding for collagens. The purpose of this study was to characterize the pathological phenotype of an OI type II-affected neonatal Holstein calf and to identify the causative genetic variant by whole-genome sequencing (WGS). The calf had acute as well as intrauterine fractures, abnormally shaped long bones and localized arthrogryposis. Genetic analysis revealed a private heterozygous missense variant in <i>COL1A1</i> (c.3917T>A) located in the fibrillar collagen NC1 domain (p.Val1306Glu) that most likely occurred de novo. This confirmed the diagnosis of OI type II and represents the first report of a pathogenic variant in the fibrillar collagen NC domain of <i>COL1A1</i> associated to OI type II in domestic animals. Furthermore, this study highlights the utility of WGS-based precise diagnostics for understanding congenital disorders in cattle and the need for continued surveillance for rare lethal genetic disorders in cattle. |
| first_indexed | 2024-03-09T00:40:52Z |
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| institution | Directory Open Access Journal |
| issn | 2076-2615 |
| language | English |
| last_indexed | 2024-03-09T00:40:52Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
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| series | Animals |
| spelling | doaj.art-a4af6be9b46c4499983650d5e86e73732023-12-11T17:49:36ZengMDPI AGAnimals2076-26152021-02-0111256110.3390/ani11020561A De Novo Mutation in <i>COL1A1</i> in a Holstein Calf with Osteogenesis Imperfecta Type IIJoana G. P. Jacinto0Irene M. Häfliger1Fintan J. McEvoy2Cord Drögemüller3Jørgen S. Agerholm4Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, ItalyInstitute of Genetics, Vetsuisse Faculty, University of Bern, 3012 Bern, SwitzerlandDepartment of Veterinary Clinical Sciences, University of Copenhagen, Dyrlægevej 16, DK 1870 Copenhagen, DenmarkInstitute of Genetics, Vetsuisse Faculty, University of Bern, 3012 Bern, SwitzerlandDepartment of Veterinary Clinical Sciences, University of Copenhagen, Dyrlægevej 16, DK 1870 Copenhagen, DenmarkOsteogenesis imperfecta (OI) type II is a genetic connective tissue disorder characterized by bone fragility, severe skeletal deformities and shortened limbs. OI usually causes perinatal death of affected individuals. OI type II diagnosis in humans is established by the identification of heterozygous mutations in genes coding for collagens. The purpose of this study was to characterize the pathological phenotype of an OI type II-affected neonatal Holstein calf and to identify the causative genetic variant by whole-genome sequencing (WGS). The calf had acute as well as intrauterine fractures, abnormally shaped long bones and localized arthrogryposis. Genetic analysis revealed a private heterozygous missense variant in <i>COL1A1</i> (c.3917T>A) located in the fibrillar collagen NC1 domain (p.Val1306Glu) that most likely occurred de novo. This confirmed the diagnosis of OI type II and represents the first report of a pathogenic variant in the fibrillar collagen NC domain of <i>COL1A1</i> associated to OI type II in domestic animals. Furthermore, this study highlights the utility of WGS-based precise diagnostics for understanding congenital disorders in cattle and the need for continued surveillance for rare lethal genetic disorders in cattle.https://www.mdpi.com/2076-2615/11/2/561cattle<i>Bos taurus</i>collagenopathyskeletal disorderbone diseaserare diseases |
| spellingShingle | Joana G. P. Jacinto Irene M. Häfliger Fintan J. McEvoy Cord Drögemüller Jørgen S. Agerholm A De Novo Mutation in <i>COL1A1</i> in a Holstein Calf with Osteogenesis Imperfecta Type II Animals cattle <i>Bos taurus</i> collagenopathy skeletal disorder bone disease rare diseases |
| title | A De Novo Mutation in <i>COL1A1</i> in a Holstein Calf with Osteogenesis Imperfecta Type II |
| title_full | A De Novo Mutation in <i>COL1A1</i> in a Holstein Calf with Osteogenesis Imperfecta Type II |
| title_fullStr | A De Novo Mutation in <i>COL1A1</i> in a Holstein Calf with Osteogenesis Imperfecta Type II |
| title_full_unstemmed | A De Novo Mutation in <i>COL1A1</i> in a Holstein Calf with Osteogenesis Imperfecta Type II |
| title_short | A De Novo Mutation in <i>COL1A1</i> in a Holstein Calf with Osteogenesis Imperfecta Type II |
| title_sort | de novo mutation in i col1a1 i in a holstein calf with osteogenesis imperfecta type ii |
| topic | cattle <i>Bos taurus</i> collagenopathy skeletal disorder bone disease rare diseases |
| url | https://www.mdpi.com/2076-2615/11/2/561 |
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