<i>LTBP3</i> Frameshift Variant in British Shorthair Cats with Complex Skeletal Dysplasia
We investigated a highly inbred family of British Shorthair cats in which two offspring were affected by deteriorating paraparesis due to complex skeletal malformations. Radiographs of both affected kittens revealed vertebral deformations with marked stenosis of the vertebral canal from T11 to L3. A...
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| Format: | Article |
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MDPI AG
2021-11-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/12/1923 |
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| author | Gabriela Rudd Garces Anna Knebel Kirsten Hülskötter Vidhya Jagannathan Theresa Störk Marion Hewicker-Trautwein Tosso Leeb Holger A. Volk |
| author_facet | Gabriela Rudd Garces Anna Knebel Kirsten Hülskötter Vidhya Jagannathan Theresa Störk Marion Hewicker-Trautwein Tosso Leeb Holger A. Volk |
| author_sort | Gabriela Rudd Garces |
| collection | DOAJ |
| description | We investigated a highly inbred family of British Shorthair cats in which two offspring were affected by deteriorating paraparesis due to complex skeletal malformations. Radiographs of both affected kittens revealed vertebral deformations with marked stenosis of the vertebral canal from T11 to L3. Additionally, compression of the spinal cord, cerebellar herniation, coprostasis and hypogangliosis were found. The pedigree suggested monogenic autosomal recessive inheritance of the trait. We sequenced the genome of an affected kitten and compared the data to 62 control genomes. This search yielded 55 private protein-changing variants of which only one was located in a likely functional candidate gene, <i>LTBP3</i>, encoding latent transforming growth factor β binding protein 3. This variant, c.158delG or p.(Gly53Alafs*16), represents a 1 bp frameshift deletion predicted to truncate 95% of the open reading frame. LTBP3 is a known key regulator of transforming growth factor β (TGF-β) and is involved in bone morphogenesis and remodeling. Genotypes at the <i>LTBP3</i>:c.158delG variant perfectly co-segregated with the phenotype in the investigated family. The available experimental data together with current knowledge on <i>LTBP3</i> variants and their functional impact in human patients and mice suggest <i>LTBP3</i>:c.158delG as a candidate causative variant for the observed skeletal malformations in British Shorthair cats. To the best of our knowledge, this study represents the first report of <i>LTBP3</i>-related complex skeletal dysplasia in domestic animals. |
| first_indexed | 2024-03-10T04:02:17Z |
| format | Article |
| id | doaj.art-52d33de8313a45ffaa19de71bd8bbb45 |
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| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T04:02:17Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-52d33de8313a45ffaa19de71bd8bbb452023-11-23T08:30:26ZengMDPI AGGenes2073-44252021-11-011212192310.3390/genes12121923<i>LTBP3</i> Frameshift Variant in British Shorthair Cats with Complex Skeletal DysplasiaGabriela Rudd Garces0Anna Knebel1Kirsten Hülskötter2Vidhya Jagannathan3Theresa Störk4Marion Hewicker-Trautwein5Tosso Leeb6Holger A. Volk7Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, SwitzerlandDepartment of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, 30559 Hannover, GermanyDepartment of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, GermanyInstitute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, SwitzerlandDepartment of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, GermanyDepartment of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, GermanyInstitute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, SwitzerlandDepartment of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, 30559 Hannover, GermanyWe investigated a highly inbred family of British Shorthair cats in which two offspring were affected by deteriorating paraparesis due to complex skeletal malformations. Radiographs of both affected kittens revealed vertebral deformations with marked stenosis of the vertebral canal from T11 to L3. Additionally, compression of the spinal cord, cerebellar herniation, coprostasis and hypogangliosis were found. The pedigree suggested monogenic autosomal recessive inheritance of the trait. We sequenced the genome of an affected kitten and compared the data to 62 control genomes. This search yielded 55 private protein-changing variants of which only one was located in a likely functional candidate gene, <i>LTBP3</i>, encoding latent transforming growth factor β binding protein 3. This variant, c.158delG or p.(Gly53Alafs*16), represents a 1 bp frameshift deletion predicted to truncate 95% of the open reading frame. LTBP3 is a known key regulator of transforming growth factor β (TGF-β) and is involved in bone morphogenesis and remodeling. Genotypes at the <i>LTBP3</i>:c.158delG variant perfectly co-segregated with the phenotype in the investigated family. The available experimental data together with current knowledge on <i>LTBP3</i> variants and their functional impact in human patients and mice suggest <i>LTBP3</i>:c.158delG as a candidate causative variant for the observed skeletal malformations in British Shorthair cats. To the best of our knowledge, this study represents the first report of <i>LTBP3</i>-related complex skeletal dysplasia in domestic animals.https://www.mdpi.com/2073-4425/12/12/1923<i>Felis catus</i>skeletal dysplasiabonedevelopmentwhole genome sequenceprecision medicine |
| spellingShingle | Gabriela Rudd Garces Anna Knebel Kirsten Hülskötter Vidhya Jagannathan Theresa Störk Marion Hewicker-Trautwein Tosso Leeb Holger A. Volk <i>LTBP3</i> Frameshift Variant in British Shorthair Cats with Complex Skeletal Dysplasia Genes <i>Felis catus</i> skeletal dysplasia bone development whole genome sequence precision medicine |
| title | <i>LTBP3</i> Frameshift Variant in British Shorthair Cats with Complex Skeletal Dysplasia |
| title_full | <i>LTBP3</i> Frameshift Variant in British Shorthair Cats with Complex Skeletal Dysplasia |
| title_fullStr | <i>LTBP3</i> Frameshift Variant in British Shorthair Cats with Complex Skeletal Dysplasia |
| title_full_unstemmed | <i>LTBP3</i> Frameshift Variant in British Shorthair Cats with Complex Skeletal Dysplasia |
| title_short | <i>LTBP3</i> Frameshift Variant in British Shorthair Cats with Complex Skeletal Dysplasia |
| title_sort | i ltbp3 i frameshift variant in british shorthair cats with complex skeletal dysplasia |
| topic | <i>Felis catus</i> skeletal dysplasia bone development whole genome sequence precision medicine |
| url | https://www.mdpi.com/2073-4425/12/12/1923 |
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