Functional characterization of five protoporphyrinogen oxidase missense mutations found in argentinean variegate porphyria patients

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 dia...

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Detalles Bibliográficos
Publicado: 2012
Materias:
Acute intermittent porphyria
Flavin adenine dinucleotide
Missense mutation
Porphyria cutanea tarda
Prokaryotic expression
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_21928304_v4_n_p91_Mendez
http://hdl.handle.net/20.500.12110/paper_21928304_v4_n_p91_Mendez
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
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spelling paper:paper_21928304_v4_n_p91_Mendez2025-07-30T19:10:42Z Functional characterization of five protoporphyrinogen oxidase missense mutations found in argentinean variegate porphyria patients Acute intermittent porphyria Flavin adenine dinucleotide Missense mutation Porphyria cutanea tarda Prokaryotic expression 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. 2012 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_21928304_v4_n_p91_Mendez http://hdl.handle.net/20.500.12110/paper_21928304_v4_n_p91_Mendez
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Acute intermittent porphyria
Flavin adenine dinucleotide
Missense mutation
Porphyria cutanea tarda
Prokaryotic expression
spellingShingle Acute intermittent porphyria
Flavin adenine dinucleotide
Missense mutation
Porphyria cutanea tarda
Prokaryotic expression
Functional characterization of five protoporphyrinogen oxidase missense mutations found in argentinean variegate porphyria patients
topic_facet Acute intermittent porphyria
Flavin adenine dinucleotide
Missense mutation
Porphyria cutanea tarda
Prokaryotic expression
description 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.
title Functional characterization of five protoporphyrinogen oxidase missense mutations found in argentinean variegate porphyria patients
title_short Functional characterization of five protoporphyrinogen oxidase missense mutations found in argentinean variegate porphyria patients
title_full Functional characterization of five protoporphyrinogen oxidase missense mutations found in argentinean variegate porphyria patients
title_fullStr Functional characterization of five protoporphyrinogen oxidase missense mutations found in argentinean variegate porphyria patients
title_full_unstemmed Functional characterization of five protoporphyrinogen oxidase missense mutations found in argentinean variegate porphyria patients
title_sort functional characterization of five protoporphyrinogen oxidase missense mutations found in argentinean variegate porphyria patients
publishDate 2012
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_21928304_v4_n_p91_Mendez
http://hdl.handle.net/20.500.12110/paper_21928304_v4_n_p91_Mendez
_version_ 1840323687828422656

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