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Abstract:

A partial deficiency in protoporphyrinogen oxidase (PPOX) produces the acute/cutaneous (or mixed) variegate porphyria (VP), the third most frequent porphyria in Argentina. This autosomal dominant disorder is clinically characterized by skin lesions and/or acute neurovisceral attacks. The precise diagnosis of patients with a symptomatic VP is essential to provide accurate treatment. It is also critical to identify asymptomatic relatives to avoid precipitating factors and prevent acute attacks. Functional consequences of five PPOX missense mutations were evaluated in a prokaryotic expression system. Three mutations were found in families previously reported c.101A>T (p.E34V), c.670T>G (W224G), c.995G>C (G332A) and two were novel findings c.227C>T (p.S76F), c.1265A>G (p.Y422C). All mutations were identified in heterozygotes with reduced PPOX activity and variable clinical expression of the disease, including asymptomatic cases. Prokaryotic expression showed that all five missense mutations decreased the PPOX activity, demonstrating their detrimental effect on enzyme function, and thus, providing evidence for their causative role in VP. These results reinforce the importance of molecular genetic analysis for VP diagnosis and especially the usefulness of prokaryotic expression of missense mutations to assess their deleterious effect on PPOX activity. MM and BXG contributed equally to the publication. RES and MVR share senior authorship. © SSIEM and Springer-Verlag Berlin Heidelberg 2011.

Registro:

Documento: Artículo
Título:Functional characterization of five protoporphyrinogen oxidase missense mutations found in argentinean variegate porphyria patients
Autor:Méndez, M.; Granata, B.X.; Jiménez, M.J.M.; Parera, V.E.; Batlle, A.; de Salamanca, R.E.; Rossetti, M.V.
Filiación:Research Center, Hospital 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain
Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), Hospital de Clínicas, CONICET-UBA, Avda. Córdoba 2351, 1er subsuelo, Buenos Aires, 1120, Argentina
Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:Acute intermittent porphyria; Flavin adenine dinucleotide; Missense mutation; Porphyria cutanea tarda; Prokaryotic expression
Año:2012
Volumen:4
Página de inicio:91
Página de fin:97
DOI: http://dx.doi.org/10.1007/8904_2011_77
Título revista:JIMD Reports
Título revista abreviado:JIMD Reports
ISSN:21928304
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_21928304_v4_n_p91_Mendez

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Citas:

---------- APA ----------
Méndez, M., Granata, B.X., Jiménez, M.J.M., Parera, V.E., Batlle, A., de Salamanca, R.E. & Rossetti, M.V. (2012) . Functional characterization of five protoporphyrinogen oxidase missense mutations found in argentinean variegate porphyria patients. JIMD Reports, 4, 91-97.
http://dx.doi.org/10.1007/8904_2011_77
---------- CHICAGO ----------
Méndez, M., Granata, B.X., Jiménez, M.J.M., Parera, V.E., Batlle, A., de Salamanca, R.E., et al. "Functional characterization of five protoporphyrinogen oxidase missense mutations found in argentinean variegate porphyria patients" . JIMD Reports 4 (2012) : 91-97.
http://dx.doi.org/10.1007/8904_2011_77
---------- MLA ----------
Méndez, M., Granata, B.X., Jiménez, M.J.M., Parera, V.E., Batlle, A., de Salamanca, R.E., et al. "Functional characterization of five protoporphyrinogen oxidase missense mutations found in argentinean variegate porphyria patients" . JIMD Reports, vol. 4, 2012, pp. 91-97.
http://dx.doi.org/10.1007/8904_2011_77
---------- VANCOUVER ----------
Méndez, M., Granata, B.X., Jiménez, M.J.M., Parera, V.E., Batlle, A., de Salamanca, R.E., et al. Functional characterization of five protoporphyrinogen oxidase missense mutations found in argentinean variegate porphyria patients. JIMD Reports. 2012;4:91-97.
http://dx.doi.org/10.1007/8904_2011_77