High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients

Detalhes bibliográficos
Autor(a) principal: Rozenberg, Roberto
Data de Publicação: 2006
Outros Autores: 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
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.
id UFSP_0fc6054096fffafcfb6b54e9c67de0d3
oai_identifier_str oai:repositorio.unifesp.br/:11600/29118
network_acronym_str UFSP
network_name_str Repositório Institucional da UNIFESP
repository_id_str 3465
spelling 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
_version_ 1814268332913721344