High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients
Autor(a) principal: | |
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Data de Publicação: | 2006 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://dx.doi.org/10.1590/S0100-879X2006000900004 http://repositorio.unifesp.br/handle/11600/29118 |
Resumo: | Gaucher disease (GD), the most prevalent lysosome storage disorder, presents an autosomal recessive mode of inheritance. It is a paradigm for therapeutic intervention in medical genetics due to the existence of effective enzyme replacement therapy. We report here the analysis of GD in 262 unrelated Brazilian patients, carried out in order to establish the frequency of the most common mutations and to provide prognostic information based on genotype-phenotype correlations. Among 247 type 1 GD patients, mutation N370S was detected in 47% of all the alleles, but N370S/N370S homozygosity was found in only 10% of the patients, a much lower frequency than expected, suggesting that most individuals presenting this genotype may not receive medical attention. Recombinant alleles were detected at a high frequency: 44% of the chromosomes bearing mutation L444P had other mutations derived from the pseudogene sequence, present in 25% of patients. Three neuronopathic type 2 patients were homozygous for L444P, all presenting additional mutations (E326K or recombinant alleles) that probably lead to the more severe phenotypes. Six children, classified as type 1 GD patients, had a L444P/L444P genotype, showing that neuronopathic symptoms may only manifest later in life. This would indicate the need for a higher treatment dose during enzyme replacement therapy. Finally, mutation G377S was present in 4 homozygous type 1 patients and also in compound heterozygosity in 5 (42%) type 3 patients. These findings indicate that G377S cannot be unambiguously classified as mild and suggest an allele-dose effect for this mutation. |
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High frequency of mutation G377S in Brazilian type 3 Gaucher disease patientsGaucher diseaseGBA geneallele dose effectGaucher disease (GD), the most prevalent lysosome storage disorder, presents an autosomal recessive mode of inheritance. It is a paradigm for therapeutic intervention in medical genetics due to the existence of effective enzyme replacement therapy. We report here the analysis of GD in 262 unrelated Brazilian patients, carried out in order to establish the frequency of the most common mutations and to provide prognostic information based on genotype-phenotype correlations. Among 247 type 1 GD patients, mutation N370S was detected in 47% of all the alleles, but N370S/N370S homozygosity was found in only 10% of the patients, a much lower frequency than expected, suggesting that most individuals presenting this genotype may not receive medical attention. Recombinant alleles were detected at a high frequency: 44% of the chromosomes bearing mutation L444P had other mutations derived from the pseudogene sequence, present in 25% of patients. Three neuronopathic type 2 patients were homozygous for L444P, all presenting additional mutations (E326K or recombinant alleles) that probably lead to the more severe phenotypes. Six children, classified as type 1 GD patients, had a L444P/L444P genotype, showing that neuronopathic symptoms may only manifest later in life. This would indicate the need for a higher treatment dose during enzyme replacement therapy. Finally, mutation G377S was present in 4 homozygous type 1 patients and also in compound heterozygosity in 5 (42%) type 3 patients. These findings indicate that G377S cannot be unambiguously classified as mild and suggest an allele-dose effect for this mutation.Univ São Paulo, Inst Biociencias, Dept Genet & Biol Evolut, BR-05508900 São Paulo, SP, BrazilHosp Evangel Londrina, Londrina, PR, BrazilHosp Base Distrito Fed, Brasilia, DF, BrazilUniv Fed Estado São Paulo, Escola Paulista Med, Dept Pediat, São Paulo, BrazilHEMORIO, Serv Hemoterapia, Rio de Janeiro, RJ, BrazilSanta Casa São Paulo, Fac Ciencias Med, Serv Hemato Oncol, São Paulo, SP, BrazilUniv Fed Estado São Paulo, Escola Paulista Med, Dept Pediat, São Paulo, BrazilWeb of ScienceAssoc Bras Divulg CientificaUniversidade de São Paulo (USP)Hosp Evangel LondrinaHosp Base Distrito FedUniversidade Federal de São Paulo (UNIFESP)HEMORIOSanta Casa São PauloRozenberg, RobertoAraujo, Fernando T.Fox, Deborah CatherineAranda, Paulo CesarNonino, AlexandreMicheletti, Cecília [UNIFESP]Martins, Ana Maria [UNIFESP]Cravo, RenataSobreira, ElisaPereira, Lygia da Veiga2016-01-24T12:41:25Z2016-01-24T12:41:25Z2006-09-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion1171-1179application/pdfhttp://dx.doi.org/10.1590/S0100-879X2006000900004Brazilian Journal of Medical and Biological Research. São Paulo: Assoc Bras Divulg Cientifica, v. 39, n. 9, p. 1171-1179, 2006.10.1590/S0100-879X20060009000040100-879XS0100-879X2006000900004http://repositorio.unifesp.br/handle/11600/29118WOS:000240545900004engBrazilian Journal of Medical and Biological Researchinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-07-31T03:49:48Zoai:repositorio.unifesp.br/:11600/29118Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-07-31T03:49:48Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.fl_str_mv |
High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients |
title |
High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients |
spellingShingle |
High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients Rozenberg, Roberto Gaucher disease GBA gene allele dose effect |
title_short |
High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients |
title_full |
High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients |
title_fullStr |
High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients |
title_full_unstemmed |
High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients |
title_sort |
High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients |
author |
Rozenberg, Roberto |
author_facet |
Rozenberg, Roberto Araujo, Fernando T. Fox, Deborah Catherine Aranda, Paulo Cesar Nonino, Alexandre Micheletti, Cecília [UNIFESP] Martins, Ana Maria [UNIFESP] Cravo, Renata Sobreira, Elisa Pereira, Lygia da Veiga |
author_role |
author |
author2 |
Araujo, Fernando T. Fox, Deborah Catherine Aranda, Paulo Cesar Nonino, Alexandre Micheletti, Cecília [UNIFESP] Martins, Ana Maria [UNIFESP] Cravo, Renata Sobreira, Elisa Pereira, Lygia da Veiga |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Hosp Evangel Londrina Hosp Base Distrito Fed Universidade Federal de São Paulo (UNIFESP) HEMORIO Santa Casa São Paulo |
dc.contributor.author.fl_str_mv |
Rozenberg, Roberto Araujo, Fernando T. Fox, Deborah Catherine Aranda, Paulo Cesar Nonino, Alexandre Micheletti, Cecília [UNIFESP] Martins, Ana Maria [UNIFESP] Cravo, Renata Sobreira, Elisa Pereira, Lygia da Veiga |
dc.subject.por.fl_str_mv |
Gaucher disease GBA gene allele dose effect |
topic |
Gaucher disease GBA gene allele dose effect |
description |
Gaucher disease (GD), the most prevalent lysosome storage disorder, presents an autosomal recessive mode of inheritance. It is a paradigm for therapeutic intervention in medical genetics due to the existence of effective enzyme replacement therapy. We report here the analysis of GD in 262 unrelated Brazilian patients, carried out in order to establish the frequency of the most common mutations and to provide prognostic information based on genotype-phenotype correlations. Among 247 type 1 GD patients, mutation N370S was detected in 47% of all the alleles, but N370S/N370S homozygosity was found in only 10% of the patients, a much lower frequency than expected, suggesting that most individuals presenting this genotype may not receive medical attention. Recombinant alleles were detected at a high frequency: 44% of the chromosomes bearing mutation L444P had other mutations derived from the pseudogene sequence, present in 25% of patients. Three neuronopathic type 2 patients were homozygous for L444P, all presenting additional mutations (E326K or recombinant alleles) that probably lead to the more severe phenotypes. Six children, classified as type 1 GD patients, had a L444P/L444P genotype, showing that neuronopathic symptoms may only manifest later in life. This would indicate the need for a higher treatment dose during enzyme replacement therapy. Finally, mutation G377S was present in 4 homozygous type 1 patients and also in compound heterozygosity in 5 (42%) type 3 patients. These findings indicate that G377S cannot be unambiguously classified as mild and suggest an allele-dose effect for this mutation. |
publishDate |
2006 |
dc.date.none.fl_str_mv |
2006-09-01 2016-01-24T12:41:25Z 2016-01-24T12:41:25Z |
dc.type.driver.fl_str_mv |
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 |
http://dx.doi.org/10.1590/S0100-879X2006000900004 Brazilian Journal of Medical and Biological Research. São Paulo: Assoc Bras Divulg Cientifica, v. 39, n. 9, p. 1171-1179, 2006. 10.1590/S0100-879X2006000900004 0100-879X S0100-879X2006000900004 http://repositorio.unifesp.br/handle/11600/29118 WOS:000240545900004 |
url |
http://dx.doi.org/10.1590/S0100-879X2006000900004 http://repositorio.unifesp.br/handle/11600/29118 |
identifier_str_mv |
Brazilian Journal of Medical and Biological Research. São Paulo: Assoc Bras Divulg Cientifica, v. 39, n. 9, p. 1171-1179, 2006. 10.1590/S0100-879X2006000900004 0100-879X S0100-879X2006000900004 WOS:000240545900004 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Brazilian Journal of Medical and Biological Research |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1171-1179 application/pdf |
dc.publisher.none.fl_str_mv |
Assoc Bras Divulg Cientifica |
publisher.none.fl_str_mv |
Assoc Bras Divulg Cientifica |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
biblioteca.csp@unifesp.br |
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1814268332913721344 |