Celia's encephalopathy and c.974dupG in BSCL2 gene: a hidden change in a known variant

Celia's encephalopathy (progressive encephalopathy with/without lipodystrophy (PELD)) is a childhood neurodegenerative disorder with a fatal prognosis before the age of 10, due to the variant c.985C>T in the BSCL2 gene that causes a cryptic splicing site leading to skipping of exon 7. For ye...

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Autores: Sánchez-Iglesias S, Crocker M, O'Callaghan M, Darling A, García-Cazorla A, Domingo-Jiménez R, Castro A, Fernández-Pombo A, Ruibal Á, Aguiar P, Garrido-Pumar M, Rodríguez-Núñez A, Álvarez-Escudero J, Brown RJ, Araújo-Vilar D
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p16105
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=16105
Access Level:acceso abierto
Palabra clave:BSCL2
PELD
Neurodegeneration
Congenital generalized lipodystrophy
Cryptic splicing
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spelling Celia's encephalopathy and c.974dupG in BSCL2 gene: a hidden change in a known variantSánchez-Iglesias SCrocker MO'Callaghan MDarling AGarcía-Cazorla ADomingo-Jiménez RCastro AFernández-Pombo ARuibal ÁAguiar PGarrido-Pumar MRodríguez-Núñez AÁlvarez-Escudero JBrown RJAraújo-Vilar DBSCL2PELDNeurodegenerationCongenital generalized lipodystrophyCryptic splicingCelia's encephalopathy (progressive encephalopathy with/without lipodystrophy (PELD)) is a childhood neurodegenerative disorder with a fatal prognosis before the age of 10, due to the variant c.985C>T in the BSCL2 gene that causes a cryptic splicing site leading to skipping of exon 7. For years, different authors have reported cases of congenital generalized lipodystrophy due to the variant c.974dupG in BSCL2 associated with neurological manifestations of variable severity, although some of them clearly superimposable to PELD. To identify the molecular mechanisms responsible for these neurological alterations in two patients with c.974dupG. Clinical characterization, biochemistry, and neuroimaging studies of two girls carrying this variant. In silico analysis, PCR amplification, and BSCL2 cDNA sequencing. BSCL2-201 transcript expression, which lacks exon 7, by qPCR in fibroblasts from the index case, from a healthy child as a control and from two patients with PELD, and in leukocytes from the index case and her parents. One with a severe encephalopathy including a picture of intellectual deficiency, severe language impairment, myoclonic epilepsy, and lipodystrophy as described in PELD, dying at 9years and 9months of age. The other 2-year-old patient showed incipient signs of neurological involvement. In silico and cDNA sequencing studies showed that variant c.974dupG gives rise to skipping of exon 7. The expression of BSCL2-201 in fibroblasts was significantly higher in the index case than in the healthy child, although less than in the case with homozygous PELD due to c.985C>T variant. The expression of this transcript was approximately half in the healthy carrier parents of this patient. The c.974dupG variant leads to the skipping of exon 7 of the BSCL2 gene and is responsible for a variant of Celia's encephalopathy, with variable phenotypic expression.SPRINGER2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=16105NEUROGENETICSISSN: 13646745ISSNe: 13646753reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p161052026-05-27T12:37:41Z
dc.title.none.fl_str_mv Celia's encephalopathy and c.974dupG in BSCL2 gene: a hidden change in a known variant
title Celia's encephalopathy and c.974dupG in BSCL2 gene: a hidden change in a known variant
spellingShingle Celia's encephalopathy and c.974dupG in BSCL2 gene: a hidden change in a known variant
Sánchez-Iglesias S
BSCL2
PELD
Neurodegeneration
Congenital generalized lipodystrophy
Cryptic splicing
title_short Celia's encephalopathy and c.974dupG in BSCL2 gene: a hidden change in a known variant
title_full Celia's encephalopathy and c.974dupG in BSCL2 gene: a hidden change in a known variant
title_fullStr Celia's encephalopathy and c.974dupG in BSCL2 gene: a hidden change in a known variant
title_full_unstemmed Celia's encephalopathy and c.974dupG in BSCL2 gene: a hidden change in a known variant
title_sort Celia's encephalopathy and c.974dupG in BSCL2 gene: a hidden change in a known variant
dc.creator.none.fl_str_mv Sánchez-Iglesias S
Crocker M
O'Callaghan M
Darling A
García-Cazorla A
Domingo-Jiménez R
Castro A
Fernández-Pombo A
Ruibal Á
Aguiar P
Garrido-Pumar M
Rodríguez-Núñez A
Álvarez-Escudero J
Brown RJ
Araújo-Vilar D
author Sánchez-Iglesias S
author_facet Sánchez-Iglesias S
Crocker M
O'Callaghan M
Darling A
García-Cazorla A
Domingo-Jiménez R
Castro A
Fernández-Pombo A
Ruibal Á
Aguiar P
Garrido-Pumar M
Rodríguez-Núñez A
Álvarez-Escudero J
Brown RJ
Araújo-Vilar D
author_role author
author2 Crocker M
O'Callaghan M
Darling A
García-Cazorla A
Domingo-Jiménez R
Castro A
Fernández-Pombo A
Ruibal Á
Aguiar P
Garrido-Pumar M
Rodríguez-Núñez A
Álvarez-Escudero J
Brown RJ
Araújo-Vilar D
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BSCL2
PELD
Neurodegeneration
Congenital generalized lipodystrophy
Cryptic splicing
topic BSCL2
PELD
Neurodegeneration
Congenital generalized lipodystrophy
Cryptic splicing
description Celia's encephalopathy (progressive encephalopathy with/without lipodystrophy (PELD)) is a childhood neurodegenerative disorder with a fatal prognosis before the age of 10, due to the variant c.985C>T in the BSCL2 gene that causes a cryptic splicing site leading to skipping of exon 7. For years, different authors have reported cases of congenital generalized lipodystrophy due to the variant c.974dupG in BSCL2 associated with neurological manifestations of variable severity, although some of them clearly superimposable to PELD. To identify the molecular mechanisms responsible for these neurological alterations in two patients with c.974dupG. Clinical characterization, biochemistry, and neuroimaging studies of two girls carrying this variant. In silico analysis, PCR amplification, and BSCL2 cDNA sequencing. BSCL2-201 transcript expression, which lacks exon 7, by qPCR in fibroblasts from the index case, from a healthy child as a control and from two patients with PELD, and in leukocytes from the index case and her parents. One with a severe encephalopathy including a picture of intellectual deficiency, severe language impairment, myoclonic epilepsy, and lipodystrophy as described in PELD, dying at 9years and 9months of age. The other 2-year-old patient showed incipient signs of neurological involvement. In silico and cDNA sequencing studies showed that variant c.974dupG gives rise to skipping of exon 7. The expression of BSCL2-201 in fibroblasts was significantly higher in the index case than in the healthy child, although less than in the case with homozygous PELD due to c.985C>T variant. The expression of this transcript was approximately half in the healthy carrier parents of this patient. The c.974dupG variant leads to the skipping of exon 7 of the BSCL2 gene and is responsible for a variant of Celia's encephalopathy, with variable phenotypic expression.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=16105
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=16105
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv SPRINGER
publisher.none.fl_str_mv SPRINGER
dc.source.none.fl_str_mv NEUROGENETICS
ISSN: 13646745
ISSNe: 13646753
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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