LTBP3 frameshift variant in british shorthair cats with complex skeletal dysplasia

Autores
Rudd Garces, Gabriela; Knebel, Anna; Hülskötter, Kirsten; Jagannathan, Vidhya; Störk, Theresa; Hewicker Trautwein, Marion; Leeb, Tosso; Volk, Holger A.
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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, LTBP3, 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 LTBP3:c.158delG variant perfectly co-segregated with the phenotype in the investigated family. The available experimental data together with current knowledge on LTBP3 variants and their functional impact in human patients and mice suggest LTBP3: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 LTBP3-related complex skeletal dysplasia in domestic animals.
Fil: Rudd Garces, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina
Fil: Knebel, Anna. University of Veterinary Medicine Hannover; Alemania
Fil: Hülskötter, Kirsten. University of Veterinary Medicine Hannover; Alemania
Fil: Jagannathan, Vidhya. University of Bern; Suiza
Fil: Störk, Theresa. University of Veterinary Medicine Hannover; Alemania
Fil: Hewicker Trautwein, Marion. University of Veterinary Medicine Hannover; Alemania
Fil: Leeb, Tosso. University of Bern; Suiza
Fil: Volk, Holger A.. University of Veterinary Medicine Hannover; Alemania
Materia
ANIMAL MODEL
BONE
DEVELOPMENT
FELIS CATUS
PRECISION MEDICINE
SKELETAL DYSPLASIA
WHOLE GENOME SEQUENCE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/212516
Acceder
id CONICETDig_1878756b8a91f6d4a2da7c93b6c4b73a
oai_identifier_str oai:ri.conicet.gov.ar:11336/212516
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling LTBP3 frameshift variant in british shorthair cats with complex skeletal dysplasiaRudd Garces, GabrielaKnebel, AnnaHülskötter, KirstenJagannathan, VidhyaStörk, TheresaHewicker Trautwein, MarionLeeb, TossoVolk, Holger A.ANIMAL MODELBONEDEVELOPMENTFELIS CATUSPRECISION MEDICINESKELETAL DYSPLASIAWHOLE GENOME SEQUENCEhttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4We 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, LTBP3, 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 LTBP3:c.158delG variant perfectly co-segregated with the phenotype in the investigated family. The available experimental data together with current knowledge on LTBP3 variants and their functional impact in human patients and mice suggest LTBP3: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 LTBP3-related complex skeletal dysplasia in domestic animals.Fil: Rudd Garces, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Knebel, Anna. University of Veterinary Medicine Hannover; AlemaniaFil: Hülskötter, Kirsten. University of Veterinary Medicine Hannover; AlemaniaFil: Jagannathan, Vidhya. University of Bern; SuizaFil: Störk, Theresa. University of Veterinary Medicine Hannover; AlemaniaFil: Hewicker Trautwein, Marion. University of Veterinary Medicine Hannover; AlemaniaFil: Leeb, Tosso. University of Bern; SuizaFil: Volk, Holger A.. University of Veterinary Medicine Hannover; AlemaniaMDPI2021-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/212516Rudd Garces, Gabriela; Knebel, Anna; Hülskötter, Kirsten; Jagannathan, Vidhya; Störk, Theresa; et al.; LTBP3 frameshift variant in british shorthair cats with complex skeletal dysplasia; MDPI; Genes; 12; 12; 12-2021; 1-112073-4425CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/genes12121923info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:18:39Zoai:ri.conicet.gov.ar:11336/212516instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:18:40.026CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv LTBP3 frameshift variant in british shorthair cats with complex skeletal dysplasia
title LTBP3 frameshift variant in british shorthair cats with complex skeletal dysplasia
spellingShingle LTBP3 frameshift variant in british shorthair cats with complex skeletal dysplasia
Rudd Garces, Gabriela
ANIMAL MODEL
BONE
DEVELOPMENT
FELIS CATUS
PRECISION MEDICINE
SKELETAL DYSPLASIA
WHOLE GENOME SEQUENCE
title_short LTBP3 frameshift variant in british shorthair cats with complex skeletal dysplasia
title_full LTBP3 frameshift variant in british shorthair cats with complex skeletal dysplasia
title_fullStr LTBP3 frameshift variant in british shorthair cats with complex skeletal dysplasia
title_full_unstemmed LTBP3 frameshift variant in british shorthair cats with complex skeletal dysplasia
title_sort LTBP3 frameshift variant in british shorthair cats with complex skeletal dysplasia
dc.creator.none.fl_str_mv Rudd Garces, Gabriela
Knebel, Anna
Hülskötter, Kirsten
Jagannathan, Vidhya
Störk, Theresa
Hewicker Trautwein, Marion
Leeb, Tosso
Volk, Holger A.
author Rudd Garces, Gabriela
author_facet Rudd Garces, Gabriela
Knebel, Anna
Hülskötter, Kirsten
Jagannathan, Vidhya
Störk, Theresa
Hewicker Trautwein, Marion
Leeb, Tosso
Volk, Holger A.
author_role author
author2 Knebel, Anna
Hülskötter, Kirsten
Jagannathan, Vidhya
Störk, Theresa
Hewicker Trautwein, Marion
Leeb, Tosso
Volk, Holger A.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANIMAL MODEL
BONE
DEVELOPMENT
FELIS CATUS
PRECISION MEDICINE
SKELETAL DYSPLASIA
WHOLE GENOME SEQUENCE
topic ANIMAL MODEL
BONE
DEVELOPMENT
FELIS CATUS
PRECISION MEDICINE
SKELETAL DYSPLASIA
WHOLE GENOME SEQUENCE
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv 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, LTBP3, 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 LTBP3:c.158delG variant perfectly co-segregated with the phenotype in the investigated family. The available experimental data together with current knowledge on LTBP3 variants and their functional impact in human patients and mice suggest LTBP3: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 LTBP3-related complex skeletal dysplasia in domestic animals.
Fil: Rudd Garces, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina
Fil: Knebel, Anna. University of Veterinary Medicine Hannover; Alemania
Fil: Hülskötter, Kirsten. University of Veterinary Medicine Hannover; Alemania
Fil: Jagannathan, Vidhya. University of Bern; Suiza
Fil: Störk, Theresa. University of Veterinary Medicine Hannover; Alemania
Fil: Hewicker Trautwein, Marion. University of Veterinary Medicine Hannover; Alemania
Fil: Leeb, Tosso. University of Bern; Suiza
Fil: Volk, Holger A.. University of Veterinary Medicine Hannover; Alemania
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, LTBP3, 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 LTBP3:c.158delG variant perfectly co-segregated with the phenotype in the investigated family. The available experimental data together with current knowledge on LTBP3 variants and their functional impact in human patients and mice suggest LTBP3: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 LTBP3-related complex skeletal dysplasia in domestic animals.
publishDate 2021
dc.date.none.fl_str_mv 2021-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/212516
Rudd Garces, Gabriela; Knebel, Anna; Hülskötter, Kirsten; Jagannathan, Vidhya; Störk, Theresa; et al.; LTBP3 frameshift variant in british shorthair cats with complex skeletal dysplasia; MDPI; Genes; 12; 12; 12-2021; 1-11
2073-4425
CONICET Digital
CONICET
url http://hdl.handle.net/11336/212516
identifier_str_mv Rudd Garces, Gabriela; Knebel, Anna; Hülskötter, Kirsten; Jagannathan, Vidhya; Störk, Theresa; et al.; LTBP3 frameshift variant in british shorthair cats with complex skeletal dysplasia; MDPI; Genes; 12; 12; 12-2021; 1-11
2073-4425
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/genes12121923
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846782619826520064
score 12.982451

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