ERYTHROPOIETIC PROTOPORPHYRIA – A Family Study and Report of a Novel Mutation in the FECH Gene
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://doi.org/10.29021/spdv.69.2.612 |
Resumo: | Erythropoietic protoporphyria (EPP) is a rare inherited disorder of heme biosynthesis caused in most patients by a deficient activity of the enzyme ferrochelatase (FECH), with a consequent accumulation of protoporphyrin (PP) in various tissues. We report a 16-year-old male (index case) with EPP characterized by acute episodes of painful photosensitivity in the photoexposed areas since his early infancy, permanent changes, microcytic anemia, thrombocytopenia and mild hepatic dysfunction. His 18-year-old sister presented slighter acute symptoms and had no chronic changes. Lesional biopsy performed in index case disclosed perivascular deposition of PAS positive hyaline material. Rimington-Cripps test was positive in both cases and PP erythrocyte levels were markedly elevated, but normal in their asymptomatic parents and younger brother. Genetic study in both patients and their mother (father’s sample not available) revealed heterozygosity for a novel mutation (c.1052delA) in FECH gene of both children, and heterozygosity for the hypomorphic allele IVS3-48T>C in all of them. This report confirms the “pseudodominant” inheritance pattern observed in most studied families, explained by the combined presence of a disabling FECH mutation and a common intronic polymorphism affecting the counterpart allele (IVS3-48T>C). The mutant allele was probably inherited from the father. This is the first description of a Portuguese family with EPP characterized at the molecular level. |
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ERYTHROPOIETIC PROTOPORPHYRIA – A Family Study and Report of a Novel Mutation in the FECH GenePROTOPORFIRIA ERITROPOIÉTICA – Caracterização de uma Família Portadora de uma Nova Mutação no Gene FECHErythropoietic protoporphyriaFerrochelataseFECHProtoporphyrinProtoporfiria eritropoiéticaFerroquelataseFECHProtoporfirinaErythropoietic protoporphyria (EPP) is a rare inherited disorder of heme biosynthesis caused in most patients by a deficient activity of the enzyme ferrochelatase (FECH), with a consequent accumulation of protoporphyrin (PP) in various tissues. We report a 16-year-old male (index case) with EPP characterized by acute episodes of painful photosensitivity in the photoexposed areas since his early infancy, permanent changes, microcytic anemia, thrombocytopenia and mild hepatic dysfunction. His 18-year-old sister presented slighter acute symptoms and had no chronic changes. Lesional biopsy performed in index case disclosed perivascular deposition of PAS positive hyaline material. Rimington-Cripps test was positive in both cases and PP erythrocyte levels were markedly elevated, but normal in their asymptomatic parents and younger brother. Genetic study in both patients and their mother (father’s sample not available) revealed heterozygosity for a novel mutation (c.1052delA) in FECH gene of both children, and heterozygosity for the hypomorphic allele IVS3-48T>C in all of them. This report confirms the “pseudodominant” inheritance pattern observed in most studied families, explained by the combined presence of a disabling FECH mutation and a common intronic polymorphism affecting the counterpart allele (IVS3-48T>C). The mutant allele was probably inherited from the father. This is the first description of a Portuguese family with EPP characterized at the molecular level.A protoporfiria eritropoiética (PPE), é uma genodermatose rara causada, na maioria dos doentes, pela redução da actividade da ferroquelatase (FECH), a última enzima da biossíntese do heme, e consequente acumulação de protoporfirina (PP) em vários tecidos. Os autores descrevem um adolescente de 16 anos (caso índice) que sofria de PPE desde a infância, caracterizada por episódios agudos de fotossensibilidade dolorosa nas áreas foto-expostas, alterações crónicas, anemia microcítica, trombocitopenia e disfunção hepática ligeira. A irmã de 18 anos apresentava sintomas agudos mais ligeiros e não evidenciava alterações crónicas. Os progenitores e o irmão mais novo eram assintomáticos. A biópsia lesional efectuada no caso índice mostrou deposição de material hialino, PAS-positivo, em localização perivascular. O teste de Rimington-Cripps foi positivo em ambos os doentes sintomáticos e os níveis de PPs eritrocitárias encontravam-se elevados, mas normais nos pais e no irmão mais novo. O estudo genético, efectuado em ambos os doentes e na mãe (amostra do pai não disponível por paradeiro desconhecido), revelou heterozigotia para uma nova mutação no gene FECH (c.1052delA) nos filhos e heterozigotia para o alelo hipomórfico IVS3-48T>C em todos os elementos testados. Confirmou-se, assim, o padrão de hereditariedade “pseudodominante” observado na maioria das famílias, explicado pela presença simultânea de uma mutação no gene FECH e de um polimorfismo frequente, afectando o alelo oposto (IVS3-48T>C). Neste caso, o alelo mutante foi provavelmente herdado do pai. Do nosso conhecimento, esta é a primeira descrição de uma família portuguesa com PPE caracterizada do ponto de vista molecular, tendo-se descrito uma nova mutação, não referida na literatura.Sociedade Portuguesa de Dermatologia e Venereologia2011-06-23T00:00:00Zjournal articleinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://doi.org/10.29021/spdv.69.2.612oai:ojs.revista.spdv.com.pt:article/612Journal of the Portuguese Society of Dermatology and Venereology; Vol 69 No 2 (2011): Abril / Junho; 247-254Revista da Sociedade Portuguesa de Dermatologia e Venereologia; v. 69 n. 2 (2011): Abril / Junho; 247-2542182-24092182-2395reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAPporhttps://revista.spdv.com.pt/index.php/spdv/article/view/612https://doi.org/10.29021/spdv.69.2.612https://revista.spdv.com.pt/index.php/spdv/article/view/612/434Morais, PauloMota, AlbertoBaudrier, TeresaFerreira, OlgaTrigo, FilipeCerqueira, RitaPalmeiro, AidaTavares, PurificaçãoAzevedo, Filomenainfo:eu-repo/semantics/openAccess2022-10-06T12:34:59ZPortal AgregadorONG |
dc.title.none.fl_str_mv |
ERYTHROPOIETIC PROTOPORPHYRIA – A Family Study and Report of a Novel Mutation in the FECH Gene PROTOPORFIRIA ERITROPOIÉTICA – Caracterização de uma Família Portadora de uma Nova Mutação no Gene FECH |
title |
ERYTHROPOIETIC PROTOPORPHYRIA – A Family Study and Report of a Novel Mutation in the FECH Gene |
spellingShingle |
ERYTHROPOIETIC PROTOPORPHYRIA – A Family Study and Report of a Novel Mutation in the FECH Gene Morais, Paulo Erythropoietic protoporphyria Ferrochelatase FECH Protoporphyrin Protoporfiria eritropoiética Ferroquelatase FECH Protoporfirina |
title_short |
ERYTHROPOIETIC PROTOPORPHYRIA – A Family Study and Report of a Novel Mutation in the FECH Gene |
title_full |
ERYTHROPOIETIC PROTOPORPHYRIA – A Family Study and Report of a Novel Mutation in the FECH Gene |
title_fullStr |
ERYTHROPOIETIC PROTOPORPHYRIA – A Family Study and Report of a Novel Mutation in the FECH Gene |
title_full_unstemmed |
ERYTHROPOIETIC PROTOPORPHYRIA – A Family Study and Report of a Novel Mutation in the FECH Gene |
title_sort |
ERYTHROPOIETIC PROTOPORPHYRIA – A Family Study and Report of a Novel Mutation in the FECH Gene |
author |
Morais, Paulo |
author_facet |
Morais, Paulo Mota, Alberto Baudrier, Teresa Ferreira, Olga Trigo, Filipe Cerqueira, Rita Palmeiro, Aida Tavares, Purificação Azevedo, Filomena |
author_role |
author |
author2 |
Mota, Alberto Baudrier, Teresa Ferreira, Olga Trigo, Filipe Cerqueira, Rita Palmeiro, Aida Tavares, Purificação Azevedo, Filomena |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Morais, Paulo Mota, Alberto Baudrier, Teresa Ferreira, Olga Trigo, Filipe Cerqueira, Rita Palmeiro, Aida Tavares, Purificação Azevedo, Filomena |
dc.subject.por.fl_str_mv |
Erythropoietic protoporphyria Ferrochelatase FECH Protoporphyrin Protoporfiria eritropoiética Ferroquelatase FECH Protoporfirina |
topic |
Erythropoietic protoporphyria Ferrochelatase FECH Protoporphyrin Protoporfiria eritropoiética Ferroquelatase FECH Protoporfirina |
description |
Erythropoietic protoporphyria (EPP) is a rare inherited disorder of heme biosynthesis caused in most patients by a deficient activity of the enzyme ferrochelatase (FECH), with a consequent accumulation of protoporphyrin (PP) in various tissues. We report a 16-year-old male (index case) with EPP characterized by acute episodes of painful photosensitivity in the photoexposed areas since his early infancy, permanent changes, microcytic anemia, thrombocytopenia and mild hepatic dysfunction. His 18-year-old sister presented slighter acute symptoms and had no chronic changes. Lesional biopsy performed in index case disclosed perivascular deposition of PAS positive hyaline material. Rimington-Cripps test was positive in both cases and PP erythrocyte levels were markedly elevated, but normal in their asymptomatic parents and younger brother. Genetic study in both patients and their mother (father’s sample not available) revealed heterozygosity for a novel mutation (c.1052delA) in FECH gene of both children, and heterozygosity for the hypomorphic allele IVS3-48T>C in all of them. This report confirms the “pseudodominant” inheritance pattern observed in most studied families, explained by the combined presence of a disabling FECH mutation and a common intronic polymorphism affecting the counterpart allele (IVS3-48T>C). The mutant allele was probably inherited from the father. This is the first description of a Portuguese family with EPP characterized at the molecular level. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-06-23T00:00:00Z |
dc.type.driver.fl_str_mv |
journal article info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://doi.org/10.29021/spdv.69.2.612 oai:ojs.revista.spdv.com.pt:article/612 |
url |
https://doi.org/10.29021/spdv.69.2.612 |
identifier_str_mv |
oai:ojs.revista.spdv.com.pt:article/612 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.none.fl_str_mv |
https://revista.spdv.com.pt/index.php/spdv/article/view/612 https://doi.org/10.29021/spdv.69.2.612 https://revista.spdv.com.pt/index.php/spdv/article/view/612/434 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Sociedade Portuguesa de Dermatologia e Venereologia |
publisher.none.fl_str_mv |
Sociedade Portuguesa de Dermatologia e Venereologia |
dc.source.none.fl_str_mv |
Journal of the Portuguese Society of Dermatology and Venereology; Vol 69 No 2 (2011): Abril / Junho; 247-254 Revista da Sociedade Portuguesa de Dermatologia e Venereologia; v. 69 n. 2 (2011): Abril / Junho; 247-254 2182-2409 2182-2395 reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
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repository.mail.fl_str_mv |
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1777301588063289344 |