NHLRC1 dodecamer repeat expansion demonstrated by whole genome sequencing in a Chihuahua with Lafora disease

Autores
Barrientos, Laura Soledad; Maiolini, Arianna; Häni, Annakatrin; Jagannathan, Vidhya; Leeb, Tosso
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Lafora disease is an autosomal recessive disor-der that causes myoclonic epilepsy.The disease is char-acterized by the presence of polyglucosan inclusion bodies (Lafora bodies), predominantly in the central nervous sys-tem. More than 90% of human Lafora disease cases arecaused by genetic variants in eitherEPM2A, encodinglaforin glucan phosphatase, orNHLRC1,encoding the NHLrepeat containing E3 ubiquitin protein ligase 1, also termedEPM2B or malin. Lafora disease in animals has similarclinical signs as the human disease, including spontaneousand reflex myoclonus, jerks and generalized tonic clonic sei-zures. Lafora disease has been reported in the dog, cat, cow and fennec fox.In dogs, Lafora disease is one of themost commonly recognized structural-metabolic epilepsiesand is inherited as an autosomal recessive condition. It ismost frequent in Miniature Wirehaired Dachshunds, BassetHounds and Beagles and has also been reported in theMiniature and Standard Poodle, Pointer and Corgi. Asingle disease-causing variant has been found in dogs. It consists of a massive expansion of a GC-rich dodecamerrepeat sequence in the canineNHLRC1gene, leading to lossof function of the gene. The wild type allele of this repeatconsists of two copies of a 12-bp motif in most mammalianspecies. In normal dogs and other canids two or threecopies are present. The pathogenic alleles leading to Laforadisease in dogs were reported to contain 14-26 copies ofthis repeat.2Genetic testing and carrier detection are notroutinely available, as the extremely GC-rich dodecamerrepeat expansion impedes PCR-based diagnostic approaches.Currently, a Southern-blot-based test is offered by theHospital for Sick Children in Toronto and represents an offi-cial DNA screening test recommended by the UK KennelClub.
Fil: Barrientos, Laura Soledad. University of Bern; Suiza. 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: Maiolini, Arianna. University of Bern; Suiza
Fil: Häni, Annakatrin. University of Bern; Suiza
Fil: Jagannathan, Vidhya. University of Bern; Suiza
Fil: Leeb, Tosso. University of Bern; Suiza
Materia
LAFORA DISEASE
GENETIC VARIANT
NHLRC1
DOGS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/121691

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network_name_str CONICET Digital (CONICET)
spelling NHLRC1 dodecamer repeat expansion demonstrated by whole genome sequencing in a Chihuahua with Lafora diseaseBarrientos, Laura SoledadMaiolini, AriannaHäni, AnnakatrinJagannathan, VidhyaLeeb, TossoLAFORA DISEASEGENETIC VARIANTNHLRC1DOGShttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4Lafora disease is an autosomal recessive disor-der that causes myoclonic epilepsy.The disease is char-acterized by the presence of polyglucosan inclusion bodies (Lafora bodies), predominantly in the central nervous sys-tem. More than 90% of human Lafora disease cases arecaused by genetic variants in eitherEPM2A, encodinglaforin glucan phosphatase, orNHLRC1,encoding the NHLrepeat containing E3 ubiquitin protein ligase 1, also termedEPM2B or malin. Lafora disease in animals has similarclinical signs as the human disease, including spontaneousand reflex myoclonus, jerks and generalized tonic clonic sei-zures. Lafora disease has been reported in the dog, cat, cow and fennec fox.In dogs, Lafora disease is one of themost commonly recognized structural-metabolic epilepsiesand is inherited as an autosomal recessive condition. It ismost frequent in Miniature Wirehaired Dachshunds, BassetHounds and Beagles and has also been reported in theMiniature and Standard Poodle, Pointer and Corgi. Asingle disease-causing variant has been found in dogs. It consists of a massive expansion of a GC-rich dodecamerrepeat sequence in the canineNHLRC1gene, leading to lossof function of the gene. The wild type allele of this repeatconsists of two copies of a 12-bp motif in most mammalianspecies. In normal dogs and other canids two or threecopies are present. The pathogenic alleles leading to Laforadisease in dogs were reported to contain 14-26 copies ofthis repeat.2Genetic testing and carrier detection are notroutinely available, as the extremely GC-rich dodecamerrepeat expansion impedes PCR-based diagnostic approaches.Currently, a Southern-blot-based test is offered by theHospital for Sick Children in Toronto and represents an offi-cial DNA screening test recommended by the UK KennelClub.Fil: Barrientos, Laura Soledad. University of Bern; Suiza. 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: Maiolini, Arianna. University of Bern; SuizaFil: Häni, Annakatrin. University of Bern; SuizaFil: Jagannathan, Vidhya. University of Bern; SuizaFil: Leeb, Tosso. University of Bern; SuizaWiley Blackwell Publishing, Inc2018-12-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/121691Barrientos, Laura Soledad; Maiolini, Arianna; Häni, Annakatrin; Jagannathan, Vidhya; Leeb, Tosso; NHLRC1 dodecamer repeat expansion demonstrated by whole genome sequencing in a Chihuahua with Lafora disease; Wiley Blackwell Publishing, Inc; Animal Genetics; 50; 1; 7-12-2018; 118-1191365-20520268-9146CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/age.12756info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/age.12756info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:39:29Zoai:ri.conicet.gov.ar:11336/121691instacron: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:34982025-09-29 09:39:29.571CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv NHLRC1 dodecamer repeat expansion demonstrated by whole genome sequencing in a Chihuahua with Lafora disease
title NHLRC1 dodecamer repeat expansion demonstrated by whole genome sequencing in a Chihuahua with Lafora disease
spellingShingle NHLRC1 dodecamer repeat expansion demonstrated by whole genome sequencing in a Chihuahua with Lafora disease
Barrientos, Laura Soledad
LAFORA DISEASE
GENETIC VARIANT
NHLRC1
DOGS
title_short NHLRC1 dodecamer repeat expansion demonstrated by whole genome sequencing in a Chihuahua with Lafora disease
title_full NHLRC1 dodecamer repeat expansion demonstrated by whole genome sequencing in a Chihuahua with Lafora disease
title_fullStr NHLRC1 dodecamer repeat expansion demonstrated by whole genome sequencing in a Chihuahua with Lafora disease
title_full_unstemmed NHLRC1 dodecamer repeat expansion demonstrated by whole genome sequencing in a Chihuahua with Lafora disease
title_sort NHLRC1 dodecamer repeat expansion demonstrated by whole genome sequencing in a Chihuahua with Lafora disease
dc.creator.none.fl_str_mv Barrientos, Laura Soledad
Maiolini, Arianna
Häni, Annakatrin
Jagannathan, Vidhya
Leeb, Tosso
author Barrientos, Laura Soledad
author_facet Barrientos, Laura Soledad
Maiolini, Arianna
Häni, Annakatrin
Jagannathan, Vidhya
Leeb, Tosso
author_role author
author2 Maiolini, Arianna
Häni, Annakatrin
Jagannathan, Vidhya
Leeb, Tosso
author2_role author
author
author
author
dc.subject.none.fl_str_mv LAFORA DISEASE
GENETIC VARIANT
NHLRC1
DOGS
topic LAFORA DISEASE
GENETIC VARIANT
NHLRC1
DOGS
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv Lafora disease is an autosomal recessive disor-der that causes myoclonic epilepsy.The disease is char-acterized by the presence of polyglucosan inclusion bodies (Lafora bodies), predominantly in the central nervous sys-tem. More than 90% of human Lafora disease cases arecaused by genetic variants in eitherEPM2A, encodinglaforin glucan phosphatase, orNHLRC1,encoding the NHLrepeat containing E3 ubiquitin protein ligase 1, also termedEPM2B or malin. Lafora disease in animals has similarclinical signs as the human disease, including spontaneousand reflex myoclonus, jerks and generalized tonic clonic sei-zures. Lafora disease has been reported in the dog, cat, cow and fennec fox.In dogs, Lafora disease is one of themost commonly recognized structural-metabolic epilepsiesand is inherited as an autosomal recessive condition. It ismost frequent in Miniature Wirehaired Dachshunds, BassetHounds and Beagles and has also been reported in theMiniature and Standard Poodle, Pointer and Corgi. Asingle disease-causing variant has been found in dogs. It consists of a massive expansion of a GC-rich dodecamerrepeat sequence in the canineNHLRC1gene, leading to lossof function of the gene. The wild type allele of this repeatconsists of two copies of a 12-bp motif in most mammalianspecies. In normal dogs and other canids two or threecopies are present. The pathogenic alleles leading to Laforadisease in dogs were reported to contain 14-26 copies ofthis repeat.2Genetic testing and carrier detection are notroutinely available, as the extremely GC-rich dodecamerrepeat expansion impedes PCR-based diagnostic approaches.Currently, a Southern-blot-based test is offered by theHospital for Sick Children in Toronto and represents an offi-cial DNA screening test recommended by the UK KennelClub.
Fil: Barrientos, Laura Soledad. University of Bern; Suiza. 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: Maiolini, Arianna. University of Bern; Suiza
Fil: Häni, Annakatrin. University of Bern; Suiza
Fil: Jagannathan, Vidhya. University of Bern; Suiza
Fil: Leeb, Tosso. University of Bern; Suiza
description Lafora disease is an autosomal recessive disor-der that causes myoclonic epilepsy.The disease is char-acterized by the presence of polyglucosan inclusion bodies (Lafora bodies), predominantly in the central nervous sys-tem. More than 90% of human Lafora disease cases arecaused by genetic variants in eitherEPM2A, encodinglaforin glucan phosphatase, orNHLRC1,encoding the NHLrepeat containing E3 ubiquitin protein ligase 1, also termedEPM2B or malin. Lafora disease in animals has similarclinical signs as the human disease, including spontaneousand reflex myoclonus, jerks and generalized tonic clonic sei-zures. Lafora disease has been reported in the dog, cat, cow and fennec fox.In dogs, Lafora disease is one of themost commonly recognized structural-metabolic epilepsiesand is inherited as an autosomal recessive condition. It ismost frequent in Miniature Wirehaired Dachshunds, BassetHounds and Beagles and has also been reported in theMiniature and Standard Poodle, Pointer and Corgi. Asingle disease-causing variant has been found in dogs. It consists of a massive expansion of a GC-rich dodecamerrepeat sequence in the canineNHLRC1gene, leading to lossof function of the gene. The wild type allele of this repeatconsists of two copies of a 12-bp motif in most mammalianspecies. In normal dogs and other canids two or threecopies are present. The pathogenic alleles leading to Laforadisease in dogs were reported to contain 14-26 copies ofthis repeat.2Genetic testing and carrier detection are notroutinely available, as the extremely GC-rich dodecamerrepeat expansion impedes PCR-based diagnostic approaches.Currently, a Southern-blot-based test is offered by theHospital for Sick Children in Toronto and represents an offi-cial DNA screening test recommended by the UK KennelClub.
publishDate 2018
dc.date.none.fl_str_mv 2018-12-07
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/11336/121691
Barrientos, Laura Soledad; Maiolini, Arianna; Häni, Annakatrin; Jagannathan, Vidhya; Leeb, Tosso; NHLRC1 dodecamer repeat expansion demonstrated by whole genome sequencing in a Chihuahua with Lafora disease; Wiley Blackwell Publishing, Inc; Animal Genetics; 50; 1; 7-12-2018; 118-119
1365-2052
0268-9146
CONICET Digital
CONICET
url http://hdl.handle.net/11336/121691
identifier_str_mv Barrientos, Laura Soledad; Maiolini, Arianna; Häni, Annakatrin; Jagannathan, Vidhya; Leeb, Tosso; NHLRC1 dodecamer repeat expansion demonstrated by whole genome sequencing in a Chihuahua with Lafora disease; Wiley Blackwell Publishing, Inc; Animal Genetics; 50; 1; 7-12-2018; 118-119
1365-2052
0268-9146
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/age.12756
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/age.12756
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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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
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