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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Sociedade Brasileira de Genética
2015
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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. |
format | Online Article Text |
id | pubmed-4415556 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Sociedade Brasileira de Genética |
record_format | MEDLINE/PubMed |
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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