Tags

Type your tag names separated by a space and hit enter

Familial porphyria cutanea tarda in Spain: characterization of eight novel mutations in the UROD gene and haplotype analysis of the common p.G281E mutation.
Gene. 2013 Jun 10; 522(1):89-95.GENE

Abstract

Porphyria cutanea tarda (PCT) results from decreased activity of uroporphyrinogen decarboxylase (UROD) in the liver. Deficiency in this enzyme results in accumulation of highly carboxylated porphyrins responsible for the disease. PCT usually occurs in adulthood and is characterized by cutaneous photosensitivity, hyperpigmentation, skin fragility and hypertrichosis. Familial PCT (F-PCT) occurs in 20-30% of patients in whom UROD gene mutations in heterozygosity decrease the enzymatic activity to about 50% in all tissues. The rare homozygous form of F-PCT (hepatoerythropoietic porphyria) has more severe clinical features and onset in childhood. In Spain, F-PCT is molecularly heterogeneous and the most frequent UROD mutation is p.G281E. In the present study, we searched for the molecular defect causing F-PCT in a group of Spanish patients and investigated whether the p.G281E mutation in the Spanish population came from a single or various origins. Among seventeen F-PCT patients, sixteen UROD mutations were identified, including eight novel ones: six missense (p.A23V, p.L78P, p.W180G, p.T196I, p.E278G and p.V279M), one frameshift (c.233delT) and one splice site mutation (c.774G>C). Prokaryotic expression studies showed the detrimental effect for each missense mutation, whereas reverse transcription-PCR and sequencing demonstrated that the novel splice site mutation caused exon 7 skipping. Moreover, haplotype analysis performed in Spanish families with the p.G281E mutation indicated that this lesion is associated with at least five haplotype backgrounds. These results extend knowledge on the molecular heterogeneity of F-PCT and suggest multiple origins of the p.G281E mutation.

Authors+Show Affiliations

Centro de Investigación, Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23545314

Citation

Gómez-Abecia, Sara, et al. "Familial Porphyria Cutanea Tarda in Spain: Characterization of Eight Novel Mutations in the UROD Gene and Haplotype Analysis of the Common p.G281E Mutation." Gene, vol. 522, no. 1, 2013, pp. 89-95.
Gómez-Abecia S, Morán-Jiménez MJ, Ruiz-Casares E, et al. Familial porphyria cutanea tarda in Spain: characterization of eight novel mutations in the UROD gene and haplotype analysis of the common p.G281E mutation. Gene. 2013;522(1):89-95.
Gómez-Abecia, S., Morán-Jiménez, M. J., Ruiz-Casares, E., Henriques-Gil, N., García-Pastor, I., Garrido-Astray, M. C., Enríquez de Salamanca, R., & Méndez, M. (2013). Familial porphyria cutanea tarda in Spain: characterization of eight novel mutations in the UROD gene and haplotype analysis of the common p.G281E mutation. Gene, 522(1), 89-95. https://doi.org/10.1016/j.gene.2013.03.074
Gómez-Abecia S, et al. Familial Porphyria Cutanea Tarda in Spain: Characterization of Eight Novel Mutations in the UROD Gene and Haplotype Analysis of the Common p.G281E Mutation. Gene. 2013 Jun 10;522(1):89-95. PubMed PMID: 23545314.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Familial porphyria cutanea tarda in Spain: characterization of eight novel mutations in the UROD gene and haplotype analysis of the common p.G281E mutation. AU - Gómez-Abecia,Sara, AU - Morán-Jiménez,María-Josefa, AU - Ruiz-Casares,Eva, AU - Henriques-Gil,Nuno, AU - García-Pastor,Inmaculada, AU - Garrido-Astray,María-Concepción, AU - Enríquez de Salamanca,Rafael, AU - Méndez,Manuel, Y1 - 2013/03/29/ PY - 2012/11/26/received PY - 2013/02/19/revised PY - 2013/03/16/accepted PY - 2013/4/3/entrez PY - 2013/4/3/pubmed PY - 2013/9/26/medline SP - 89 EP - 95 JF - Gene JO - Gene VL - 522 IS - 1 N2 - Porphyria cutanea tarda (PCT) results from decreased activity of uroporphyrinogen decarboxylase (UROD) in the liver. Deficiency in this enzyme results in accumulation of highly carboxylated porphyrins responsible for the disease. PCT usually occurs in adulthood and is characterized by cutaneous photosensitivity, hyperpigmentation, skin fragility and hypertrichosis. Familial PCT (F-PCT) occurs in 20-30% of patients in whom UROD gene mutations in heterozygosity decrease the enzymatic activity to about 50% in all tissues. The rare homozygous form of F-PCT (hepatoerythropoietic porphyria) has more severe clinical features and onset in childhood. In Spain, F-PCT is molecularly heterogeneous and the most frequent UROD mutation is p.G281E. In the present study, we searched for the molecular defect causing F-PCT in a group of Spanish patients and investigated whether the p.G281E mutation in the Spanish population came from a single or various origins. Among seventeen F-PCT patients, sixteen UROD mutations were identified, including eight novel ones: six missense (p.A23V, p.L78P, p.W180G, p.T196I, p.E278G and p.V279M), one frameshift (c.233delT) and one splice site mutation (c.774G>C). Prokaryotic expression studies showed the detrimental effect for each missense mutation, whereas reverse transcription-PCR and sequencing demonstrated that the novel splice site mutation caused exon 7 skipping. Moreover, haplotype analysis performed in Spanish families with the p.G281E mutation indicated that this lesion is associated with at least five haplotype backgrounds. These results extend knowledge on the molecular heterogeneity of F-PCT and suggest multiple origins of the p.G281E mutation. SN - 1879-0038 UR - https://www.unboundmedicine.com/medline/citation/23545314/Familial_porphyria_cutanea_tarda_in_Spain:_characterization_of_eight_novel_mutations_in_the_UROD_gene_and_haplotype_analysis_of_the_common_p_G281E_mutation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-1119(13)00343-0 DB - PRIME DP - Unbound Medicine ER -