Novel splice-affecting variants in CYP27A1 gene in two Chilean patients with Cerebrotendinous Xanthomatosis
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , , |
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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Genetics and Molecular Biology |
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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 |
_version_ |
1752122386258329600 |