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

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 catara...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Sociedade Brasileira de Genética 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415556/
https://www.ncbi.nlm.nih.gov/pubmed/25983621
http://dx.doi.org/10.1590/S1415-475738120140087
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author 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_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_sort Smalley, Susan V.
collection PubMed
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.
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spelling pubmed-44155562015-05-15 Novel splice-affecting variants in CYP27A1 gene in two Chilean patients with Cerebrotendinous Xanthomatosis 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 Genet Mol Biol Human and Medical Genetics 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. Sociedade Brasileira de Genética 2015-03 2014-03-17 /pmc/articles/PMC4415556/ /pubmed/25983621 http://dx.doi.org/10.1590/S1415-475738120140087 Text en Copyright © 2015, Sociedade Brasileira de Genética. http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Human and Medical Genetics
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
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
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_short 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
topic Human and Medical Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415556/
https://www.ncbi.nlm.nih.gov/pubmed/25983621
http://dx.doi.org/10.1590/S1415-475738120140087
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