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Identification and characterization of HMBS gene mutations in Spanish patients with acute intermittent porphyria

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dc.contributor.author Méndez, Manuel spa
dc.contributor.author Morán-Jiménez, María Josefa spa
dc.contributor.author Gómez-Abecia, S. spa
dc.contributor.author García-Bravo, María spa
dc.contributor.author Garrido Astray, María Concepción spa
dc.contributor.author Fontanellas, Antonio spa
dc.contributor.author Poblete-Gutiérrez, Pamela spa
dc.contributor.author Frank, Jorge spa
dc.contributor.author Enríquez de Salamanca, Rafael spa
dc.date.accessioned 2013-11-27T17:26:36Z
dc.date.available 2013-11-27T17:26:36Z
dc.date.issued 2009 spa
dc.identifier.citation Méndez, M., Morán-Jiménez, M. J., Gómez-Abecia, S., García-Bravo, M., Garrido-Astray, M. C., Fontanellas, A., ..., & Enríquez-Salamanca, R. (2008). Identification and characterization of HMBS gene mutations in Spanish patients with acute intermittent porphyria. Cellular and Molecular Biology, 55(2), 55-63. spa
dc.identifier.uri http://hdl.handle.net/11268/888
dc.description.abstract Acute intermittent porphyria (AIP), the most common acute hepatic porphyria, is an autosomal dominant disorder with low penetrance that results from a partial deficiency of hydroxymethylbilane synthase (HMBS), the third enzyme in the heme biosynthetic pathway. The disease is clinically characterized by acute neurovisceral attacks that are precipitated by several factors including certain drugs, steroid hormones, alcohol and fasting. Early diagnosis and counselling are essential to prevent attacks, being mutation analysis the most reliable method to identify asymptomatic carriers in AIP families. In this study we have investigated the molecular defect in 15 unrelated Spanish AIP patients. Mutation analysis of the HMBS gene revealed a total of fourteen mutations including six novel ones, two of them were on the same allele in one patient. The novel mutations were three missense (R26L, R173G and D178H), two frameshift (c.749_765dup and c.874insC) and one intronic deletion (IVS12+3_+11delAGGGCCTGT).RT-PCR and sequencing demonstrated that the intronic mutation caused abnormal splicing and exon 12 skipping. Prokaryotic expression of the novel missense mutations showed that only D178H had significant residual activity. These findings will facilitate the accurate identification of presymptomatic AIP carriers in these families and they further emphasize the molecular heterogeneity of AIP in Spain. spa
dc.language.iso spa spa
dc.title Identification and characterization of HMBS gene mutations in Spanish patients with acute intermittent porphyria spa
dc.type article spa
dc.description.impact 1.176 JCR (2009) Q4, 237/283 Biochemistry & molecular biology, 144/162 Cell biology spa
dc.rights.accessRights closedAccess en
dc.subject.unesco Genética humana spa
dc.peerreviewed Si spa


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