New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutations

Autores
Ramos, Mónica; Menao, Sebastián; Arnedo, María; Puisac, Beatriz; Gil Rodríguez, María Concepción; Teresa Rodrigo, María Esperanza; Hernández Marcos, María; Pierre, Germaine; Ramaswami, Uma; Baquero Montoya, Carolina; Bueno, Gloria; Casale, Cesar Horacio; Hegardt, Fausto G.; Gómez Puertas, Paulino; Pié, Juan
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mitochondrial HMG-CoA synthase deficiency is a rare inherited metabolic disorder that affects ketone-body synthesis. Acute episodes include vomiting, lethargy, hepatomegaly, hypoglycaemia, dicarboxylic aciduria, and in severe cases, coma. This deficiency may have been under-diagnosed owing to the absence of specific clinical and biochemical markers, limitations in liver biopsy and the lack of an effective method of expression and enzyme assay for verifying the mutations found. To date, eight patients have been reported with nine allelic variants of the HMGCS2 gene. We present a new method of enzyme expression and a modification of the activity assay that allows, for first time, the functional study of missense mutations found in patients with this deficiency. Four of the missense mutations (p.V54M, p.R188H, p.G212R and p.G388R) did not produce proteins that could have been detected in soluble form by western blot; three produced a total loss of activity (p.Y167C, p.M307T and p.R500H) and one, variant p.F174L, gave an enzyme with a catalytic efficiency of 11.5%. This indicates that the deficiency may occur with partial loss of activity of enzyme. In addition, we describe a new patient with this deficiency, in which we detected the missense allelic variant, c.1162G>A (p.G388R) and the nonsense variant c.1270C>T (p.R424X).
Fil: Ramos, Mónica. Universidad de Zaragoza; España
Fil: Menao, Sebastián. Universidad de Zaragoza; España
Fil: Arnedo, María. Universidad de Zaragoza; España
Fil: Puisac, Beatriz. Universidad de Zaragoza; España
Fil: Gil Rodríguez, María Concepción. Universidad de Zaragoza; España
Fil: Teresa Rodrigo, María Esperanza. Universidad de Zaragoza; España
Fil: Hernández Marcos, María. Universidad de Zaragoza; España
Fil: Pierre, Germaine. Birmingham Children’s Hospital; Reino Unido
Fil: Ramaswami, Uma. Central Manchester University Hospitals; Reino Unido
Fil: Baquero Montoya, Carolina. Universidad de Zaragoza; España
Fil: Bueno, Gloria. Universidad de Zaragoza; España
Fil: Casale, Cesar Horacio. Universidad de Zaragoza; España. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Hegardt, Fausto G.. Universidad de Barcelona; España
Fil: Gómez Puertas, Paulino. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; España
Fil: Pié, Juan. Universidad de Zaragoza; España
Materia
Mitochondrial Hmg-Coa Synthase Deficiency
Mutations
Ketone Bodies
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/24671
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/24671
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutationsRamos, MónicaMenao, SebastiánArnedo, MaríaPuisac, BeatrizGil Rodríguez, María ConcepciónTeresa Rodrigo, María EsperanzaHernández Marcos, MaríaPierre, GermaineRamaswami, UmaBaquero Montoya, CarolinaBueno, GloriaCasale, Cesar HoracioHegardt, Fausto G.Gómez Puertas, PaulinoPié, JuanMitochondrial Hmg-Coa Synthase DeficiencyMutationsKetone Bodieshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Mitochondrial HMG-CoA synthase deficiency is a rare inherited metabolic disorder that affects ketone-body synthesis. Acute episodes include vomiting, lethargy, hepatomegaly, hypoglycaemia, dicarboxylic aciduria, and in severe cases, coma. This deficiency may have been under-diagnosed owing to the absence of specific clinical and biochemical markers, limitations in liver biopsy and the lack of an effective method of expression and enzyme assay for verifying the mutations found. To date, eight patients have been reported with nine allelic variants of the HMGCS2 gene. We present a new method of enzyme expression and a modification of the activity assay that allows, for first time, the functional study of missense mutations found in patients with this deficiency. Four of the missense mutations (p.V54M, p.R188H, p.G212R and p.G388R) did not produce proteins that could have been detected in soluble form by western blot; three produced a total loss of activity (p.Y167C, p.M307T and p.R500H) and one, variant p.F174L, gave an enzyme with a catalytic efficiency of 11.5%. This indicates that the deficiency may occur with partial loss of activity of enzyme. In addition, we describe a new patient with this deficiency, in which we detected the missense allelic variant, c.1162G>A (p.G388R) and the nonsense variant c.1270C>T (p.R424X).Fil: Ramos, Mónica. Universidad de Zaragoza; EspañaFil: Menao, Sebastián. Universidad de Zaragoza; EspañaFil: Arnedo, María. Universidad de Zaragoza; EspañaFil: Puisac, Beatriz. Universidad de Zaragoza; EspañaFil: Gil Rodríguez, María Concepción. Universidad de Zaragoza; EspañaFil: Teresa Rodrigo, María Esperanza. Universidad de Zaragoza; EspañaFil: Hernández Marcos, María. Universidad de Zaragoza; EspañaFil: Pierre, Germaine. Birmingham Children’s Hospital; Reino UnidoFil: Ramaswami, Uma. Central Manchester University Hospitals; Reino UnidoFil: Baquero Montoya, Carolina. Universidad de Zaragoza; EspañaFil: Bueno, Gloria. Universidad de Zaragoza; EspañaFil: Casale, Cesar Horacio. Universidad de Zaragoza; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Hegardt, Fausto G.. Universidad de Barcelona; EspañaFil: Gómez Puertas, Paulino. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; EspañaFil: Pié, Juan. Universidad de Zaragoza; EspañaElsevier Masson2013-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/24671Ramos, Mónica; Menao, Sebastián; Arnedo, María; Puisac, Beatriz; Gil Rodríguez, María Concepción; et al.; New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutations; Elsevier Masson; European Journal Of Medical Genetics; 56; 8; 6-2013; 411-4151769-7212CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejmg.2013.05.008info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1769721213001262info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:50:00Zoai:ri.conicet.gov.ar:11336/24671instacron: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 09:50:00.71CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutations
title New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutations
spellingShingle New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutations
Ramos, Mónica
Mitochondrial Hmg-Coa Synthase Deficiency
Mutations
Ketone Bodies
title_short New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutations
title_full New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutations
title_fullStr New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutations
title_full_unstemmed New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutations
title_sort New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutations
dc.creator.none.fl_str_mv Ramos, Mónica
Menao, Sebastián
Arnedo, María
Puisac, Beatriz
Gil Rodríguez, María Concepción
Teresa Rodrigo, María Esperanza
Hernández Marcos, María
Pierre, Germaine
Ramaswami, Uma
Baquero Montoya, Carolina
Bueno, Gloria
Casale, Cesar Horacio
Hegardt, Fausto G.
Gómez Puertas, Paulino
Pié, Juan
author Ramos, Mónica
author_facet Ramos, Mónica
Menao, Sebastián
Arnedo, María
Puisac, Beatriz
Gil Rodríguez, María Concepción
Teresa Rodrigo, María Esperanza
Hernández Marcos, María
Pierre, Germaine
Ramaswami, Uma
Baquero Montoya, Carolina
Bueno, Gloria
Casale, Cesar Horacio
Hegardt, Fausto G.
Gómez Puertas, Paulino
Pié, Juan
author_role author
author2 Menao, Sebastián
Arnedo, María
Puisac, Beatriz
Gil Rodríguez, María Concepción
Teresa Rodrigo, María Esperanza
Hernández Marcos, María
Pierre, Germaine
Ramaswami, Uma
Baquero Montoya, Carolina
Bueno, Gloria
Casale, Cesar Horacio
Hegardt, Fausto G.
Gómez Puertas, Paulino
Pié, Juan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mitochondrial Hmg-Coa Synthase Deficiency
Mutations
Ketone Bodies
topic Mitochondrial Hmg-Coa Synthase Deficiency
Mutations
Ketone Bodies
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Mitochondrial HMG-CoA synthase deficiency is a rare inherited metabolic disorder that affects ketone-body synthesis. Acute episodes include vomiting, lethargy, hepatomegaly, hypoglycaemia, dicarboxylic aciduria, and in severe cases, coma. This deficiency may have been under-diagnosed owing to the absence of specific clinical and biochemical markers, limitations in liver biopsy and the lack of an effective method of expression and enzyme assay for verifying the mutations found. To date, eight patients have been reported with nine allelic variants of the HMGCS2 gene. We present a new method of enzyme expression and a modification of the activity assay that allows, for first time, the functional study of missense mutations found in patients with this deficiency. Four of the missense mutations (p.V54M, p.R188H, p.G212R and p.G388R) did not produce proteins that could have been detected in soluble form by western blot; three produced a total loss of activity (p.Y167C, p.M307T and p.R500H) and one, variant p.F174L, gave an enzyme with a catalytic efficiency of 11.5%. This indicates that the deficiency may occur with partial loss of activity of enzyme. In addition, we describe a new patient with this deficiency, in which we detected the missense allelic variant, c.1162G>A (p.G388R) and the nonsense variant c.1270C>T (p.R424X).
Fil: Ramos, Mónica. Universidad de Zaragoza; España
Fil: Menao, Sebastián. Universidad de Zaragoza; España
Fil: Arnedo, María. Universidad de Zaragoza; España
Fil: Puisac, Beatriz. Universidad de Zaragoza; España
Fil: Gil Rodríguez, María Concepción. Universidad de Zaragoza; España
Fil: Teresa Rodrigo, María Esperanza. Universidad de Zaragoza; España
Fil: Hernández Marcos, María. Universidad de Zaragoza; España
Fil: Pierre, Germaine. Birmingham Children’s Hospital; Reino Unido
Fil: Ramaswami, Uma. Central Manchester University Hospitals; Reino Unido
Fil: Baquero Montoya, Carolina. Universidad de Zaragoza; España
Fil: Bueno, Gloria. Universidad de Zaragoza; España
Fil: Casale, Cesar Horacio. Universidad de Zaragoza; España. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Hegardt, Fausto G.. Universidad de Barcelona; España
Fil: Gómez Puertas, Paulino. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; España
Fil: Pié, Juan. Universidad de Zaragoza; España
description Mitochondrial HMG-CoA synthase deficiency is a rare inherited metabolic disorder that affects ketone-body synthesis. Acute episodes include vomiting, lethargy, hepatomegaly, hypoglycaemia, dicarboxylic aciduria, and in severe cases, coma. This deficiency may have been under-diagnosed owing to the absence of specific clinical and biochemical markers, limitations in liver biopsy and the lack of an effective method of expression and enzyme assay for verifying the mutations found. To date, eight patients have been reported with nine allelic variants of the HMGCS2 gene. We present a new method of enzyme expression and a modification of the activity assay that allows, for first time, the functional study of missense mutations found in patients with this deficiency. Four of the missense mutations (p.V54M, p.R188H, p.G212R and p.G388R) did not produce proteins that could have been detected in soluble form by western blot; three produced a total loss of activity (p.Y167C, p.M307T and p.R500H) and one, variant p.F174L, gave an enzyme with a catalytic efficiency of 11.5%. This indicates that the deficiency may occur with partial loss of activity of enzyme. In addition, we describe a new patient with this deficiency, in which we detected the missense allelic variant, c.1162G>A (p.G388R) and the nonsense variant c.1270C>T (p.R424X).
publishDate 2013
dc.date.none.fl_str_mv 2013-06
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/11336/24671
Ramos, Mónica; Menao, Sebastián; Arnedo, María; Puisac, Beatriz; Gil Rodríguez, María Concepción; et al.; New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutations; Elsevier Masson; European Journal Of Medical Genetics; 56; 8; 6-2013; 411-415
1769-7212
CONICET Digital
CONICET
url http://hdl.handle.net/11336/24671
identifier_str_mv Ramos, Mónica; Menao, Sebastián; Arnedo, María; Puisac, Beatriz; Gil Rodríguez, María Concepción; et al.; New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutations; Elsevier Masson; European Journal Of Medical Genetics; 56; 8; 6-2013; 411-415
1769-7212
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejmg.2013.05.008
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1769721213001262
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Masson
publisher.none.fl_str_mv Elsevier Masson
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
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score 13.070432

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