Novel splice-affecting variants in CYP27A1 gene in two Chilean patients with Cerebrotendinous Xanthomatosis

Detalhes bibliográficos
Autor(a) principal: Smalley,Susan V.
Data de Publicação: 2015
Outros Autores: Preiss,Yudith, Suazo,José, Vega,Javier Andrés, Angellotti,Isidora, Lagos,Carlos F., Rivera,Enzo, Kleinsteuber,Karin, Campion,Javier, Martínez,J. Alfredo, Maiz,Alberto, Santos,José Luis
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Genetics and Molecular Biology
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572015000100030
Resumo: Cerebrotendinous Xanthomatosis (CTX), a rare lipid storage disorder, is caused by recessive loss-of-function mutations of the 27-sterol hydroxylase (CYP27A1), producing an alteration of the synthesis of bile acids, with an accumulation of cholestanol. Clinical characteristics include juvenile cataracts, diarrhea, tendon xanthomas, cognitive impairment and other neurological manifestations. Early diagnosis is critical, because treatment with chenodeoxycholic acid may prevent neurological damage. We studied the CYP27A1 gene in two Chilean CTX patients by sequencing its nine exons, exon-intron boundaries, and cDNA from peripheral blood mononuclear cells. Patient 1 is a compound heterozygote for the novel substitution c.256-1G > T that causes exon 2 skipping, leading to a premature stop codon in exon 3, and for the previously-known pathogenic mutation c.1183C > T (p.Arg395Cys). Patient 2 is homozygous for the novel mutation c.1185-1G > A that causes exon 7 skipping and the generation of a premature stop codon in exon 8, leading to the loss of the crucial adrenoxin binding domain of CYP27A1.
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spelling Novel splice-affecting variants in CYP27A1 gene in two Chilean patients with Cerebrotendinous XanthomatosisCerebrotendinous Xanthomatosissplicingmutationexon skippingCerebrotendinous Xanthomatosis (CTX), a rare lipid storage disorder, is caused by recessive loss-of-function mutations of the 27-sterol hydroxylase (CYP27A1), producing an alteration of the synthesis of bile acids, with an accumulation of cholestanol. Clinical characteristics include juvenile cataracts, diarrhea, tendon xanthomas, cognitive impairment and other neurological manifestations. Early diagnosis is critical, because treatment with chenodeoxycholic acid may prevent neurological damage. We studied the CYP27A1 gene in two Chilean CTX patients by sequencing its nine exons, exon-intron boundaries, and cDNA from peripheral blood mononuclear cells. Patient 1 is a compound heterozygote for the novel substitution c.256-1G > T that causes exon 2 skipping, leading to a premature stop codon in exon 3, and for the previously-known pathogenic mutation c.1183C > T (p.Arg395Cys). Patient 2 is homozygous for the novel mutation c.1185-1G > A that causes exon 7 skipping and the generation of a premature stop codon in exon 8, leading to the loss of the crucial adrenoxin binding domain of CYP27A1.Sociedade Brasileira de Genética2015-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572015000100030Genetics and Molecular Biology v.38 n.1 2015reponame:Genetics and Molecular Biologyinstname:Sociedade Brasileira de Genética (SBG)instacron:SBG10.1590/S1415-475738120140087info:eu-repo/semantics/openAccessSmalley,Susan V.Preiss,YudithSuazo,JoséVega,Javier AndrésAngellotti,IsidoraLagos,Carlos F.Rivera,EnzoKleinsteuber,KarinCampion,JavierMartínez,J. AlfredoMaiz,AlbertoSantos,José Luiseng2015-04-22T00:00:00Zoai:scielo:S1415-47572015000100030Revistahttp://www.gmb.org.br/ONGhttps://old.scielo.br/oai/scielo-oai.php||editor@gmb.org.br1678-46851415-4757opendoar:2015-04-22T00:00Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG)false
dc.title.none.fl_str_mv Novel splice-affecting variants in CYP27A1 gene in two Chilean patients with Cerebrotendinous Xanthomatosis
title Novel splice-affecting variants in CYP27A1 gene in two Chilean patients with Cerebrotendinous Xanthomatosis
spellingShingle Novel splice-affecting variants in CYP27A1 gene in two Chilean patients with Cerebrotendinous Xanthomatosis
Smalley,Susan V.
Cerebrotendinous Xanthomatosis
splicing
mutation
exon skipping
title_short Novel splice-affecting variants in CYP27A1 gene in two Chilean patients with Cerebrotendinous Xanthomatosis
title_full Novel splice-affecting variants in CYP27A1 gene in two Chilean patients with Cerebrotendinous Xanthomatosis
title_fullStr Novel splice-affecting variants in CYP27A1 gene in two Chilean patients with Cerebrotendinous Xanthomatosis
title_full_unstemmed Novel splice-affecting variants in CYP27A1 gene in two Chilean patients with Cerebrotendinous Xanthomatosis
title_sort Novel splice-affecting variants in CYP27A1 gene in two Chilean patients with Cerebrotendinous Xanthomatosis
author Smalley,Susan V.
author_facet Smalley,Susan V.
Preiss,Yudith
Suazo,José
Vega,Javier Andrés
Angellotti,Isidora
Lagos,Carlos F.
Rivera,Enzo
Kleinsteuber,Karin
Campion,Javier
Martínez,J. Alfredo
Maiz,Alberto
Santos,José Luis
author_role author
author2 Preiss,Yudith
Suazo,José
Vega,Javier Andrés
Angellotti,Isidora
Lagos,Carlos F.
Rivera,Enzo
Kleinsteuber,Karin
Campion,Javier
Martínez,J. Alfredo
Maiz,Alberto
Santos,José Luis
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Smalley,Susan V.
Preiss,Yudith
Suazo,José
Vega,Javier Andrés
Angellotti,Isidora
Lagos,Carlos F.
Rivera,Enzo
Kleinsteuber,Karin
Campion,Javier
Martínez,J. Alfredo
Maiz,Alberto
Santos,José Luis
dc.subject.por.fl_str_mv Cerebrotendinous Xanthomatosis
splicing
mutation
exon skipping
topic Cerebrotendinous Xanthomatosis
splicing
mutation
exon skipping
description Cerebrotendinous Xanthomatosis (CTX), a rare lipid storage disorder, is caused by recessive loss-of-function mutations of the 27-sterol hydroxylase (CYP27A1), producing an alteration of the synthesis of bile acids, with an accumulation of cholestanol. Clinical characteristics include juvenile cataracts, diarrhea, tendon xanthomas, cognitive impairment and other neurological manifestations. Early diagnosis is critical, because treatment with chenodeoxycholic acid may prevent neurological damage. We studied the CYP27A1 gene in two Chilean CTX patients by sequencing its nine exons, exon-intron boundaries, and cDNA from peripheral blood mononuclear cells. Patient 1 is a compound heterozygote for the novel substitution c.256-1G > T that causes exon 2 skipping, leading to a premature stop codon in exon 3, and for the previously-known pathogenic mutation c.1183C > T (p.Arg395Cys). Patient 2 is homozygous for the novel mutation c.1185-1G > A that causes exon 7 skipping and the generation of a premature stop codon in exon 8, leading to the loss of the crucial adrenoxin binding domain of CYP27A1.
publishDate 2015
dc.date.none.fl_str_mv 2015-03-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572015000100030
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572015000100030
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1590/S1415-475738120140087
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Sociedade Brasileira de Genética
publisher.none.fl_str_mv Sociedade Brasileira de Genética
dc.source.none.fl_str_mv Genetics and Molecular Biology v.38 n.1 2015
reponame:Genetics and Molecular Biology
instname:Sociedade Brasileira de Genética (SBG)
instacron:SBG
instname_str Sociedade Brasileira de Genética (SBG)
instacron_str SBG
institution SBG
reponame_str Genetics and Molecular Biology
collection Genetics and Molecular Biology
repository.name.fl_str_mv Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG)
repository.mail.fl_str_mv ||editor@gmb.org.br
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