CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population

Detalhes bibliográficos
Autor(a) principal: Ferreira, Filipa
Data de Publicação: 2018
Outros Autores: Leal, Inês, Sousa, David, Costa, Teresa, Mota, Conceição, Gomes, Ana Marta, Lopes, Daniela, Carmo Macário, Maria do, Tavares, Isabel, Pinto, Helena, Oliveira, João Paulo, Magriço, Rita, Carmona, Célia, Ramos, Sónia, Neiva, Raquel, Marcão, Ana, Vilarinho, Laura
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/6305
Resumo: Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective : This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene . Methods : Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS , followed by direct sequencing of the coding exons of CTNS . Results : From 1998 to 2017, twenty-one cystinotic patients were biochemically diagnosed. From the remaining seventeen (four deceased), eleven were studied for CTNS gene. Five out of eleven patients were homozygous for the 57-kb deletion (10/22; 45.5%), and other five were compound heterozygous for this variant (15/22; 68.2%). The other mutations found were p.Q128X (c.721 C>T; 2/22), p.S139F (c.755 C>T; 4/22) and c.18-21delGACT (p.T7FfsX7; 1/22). All of these seventeen cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions: The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in our country and it could be the basis for future genetic counseling in Portuguese population.
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spelling CTNS Molecular Genetics Profile in a Portuguese Cystinosis PopulationCystinosisCTNS GeneMutational SpectrumKidney Failure57-kbDeletionMolecular Genetics ProfilePortuguese PopulationDoenças GenéticasBackground: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective : This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene . Methods : Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS , followed by direct sequencing of the coding exons of CTNS . Results : From 1998 to 2017, twenty-one cystinotic patients were biochemically diagnosed. From the remaining seventeen (four deceased), eleven were studied for CTNS gene. Five out of eleven patients were homozygous for the 57-kb deletion (10/22; 45.5%), and other five were compound heterozygous for this variant (15/22; 68.2%). The other mutations found were p.Q128X (c.721 C>T; 2/22), p.S139F (c.755 C>T; 4/22) and c.18-21delGACT (p.T7FfsX7; 1/22). All of these seventeen cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions: The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in our country and it could be the basis for future genetic counseling in Portuguese population.Scientific Research PublishingRepositório Científico do Instituto Nacional de SaúdeFerreira, FilipaLeal, InêsSousa, DavidCosta, TeresaMota, ConceiçãoGomes, Ana MartaLopes, DanielaCarmo Macário, Maria doTavares, IsabelPinto, HelenaOliveira, João PauloMagriço, RitaCarmona, CéliaRamos, SóniaNeiva, RaquelMarcão, AnaVilarinho, Laura2019-03-25T17:29:16Z2018-12-282018-12-28T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/6305engOpen J Genet. 2018;8(4):91-100. doi:10.4236/ojgen.2018.840082162-445310.4236/ojgen.2018.84008info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:41:20Zoai:repositorio.insa.pt:10400.18/6305Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:40:57.185682Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population
title CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population
spellingShingle CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population
Ferreira, Filipa
Cystinosis
CTNS Gene
Mutational Spectrum
Kidney Failure
57-kb
Deletion
Molecular Genetics Profile
Portuguese Population
Doenças Genéticas
title_short CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population
title_full CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population
title_fullStr CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population
title_full_unstemmed CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population
title_sort CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population
author Ferreira, Filipa
author_facet Ferreira, Filipa
Leal, Inês
Sousa, David
Costa, Teresa
Mota, Conceição
Gomes, Ana Marta
Lopes, Daniela
Carmo Macário, Maria do
Tavares, Isabel
Pinto, Helena
Oliveira, João Paulo
Magriço, Rita
Carmona, Célia
Ramos, Sónia
Neiva, Raquel
Marcão, Ana
Vilarinho, Laura
author_role author
author2 Leal, Inês
Sousa, David
Costa, Teresa
Mota, Conceição
Gomes, Ana Marta
Lopes, Daniela
Carmo Macário, Maria do
Tavares, Isabel
Pinto, Helena
Oliveira, João Paulo
Magriço, Rita
Carmona, Célia
Ramos, Sónia
Neiva, Raquel
Marcão, Ana
Vilarinho, Laura
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Ferreira, Filipa
Leal, Inês
Sousa, David
Costa, Teresa
Mota, Conceição
Gomes, Ana Marta
Lopes, Daniela
Carmo Macário, Maria do
Tavares, Isabel
Pinto, Helena
Oliveira, João Paulo
Magriço, Rita
Carmona, Célia
Ramos, Sónia
Neiva, Raquel
Marcão, Ana
Vilarinho, Laura
dc.subject.por.fl_str_mv Cystinosis
CTNS Gene
Mutational Spectrum
Kidney Failure
57-kb
Deletion
Molecular Genetics Profile
Portuguese Population
Doenças Genéticas
topic Cystinosis
CTNS Gene
Mutational Spectrum
Kidney Failure
57-kb
Deletion
Molecular Genetics Profile
Portuguese Population
Doenças Genéticas
description Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective : This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene . Methods : Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS , followed by direct sequencing of the coding exons of CTNS . Results : From 1998 to 2017, twenty-one cystinotic patients were biochemically diagnosed. From the remaining seventeen (four deceased), eleven were studied for CTNS gene. Five out of eleven patients were homozygous for the 57-kb deletion (10/22; 45.5%), and other five were compound heterozygous for this variant (15/22; 68.2%). The other mutations found were p.Q128X (c.721 C>T; 2/22), p.S139F (c.755 C>T; 4/22) and c.18-21delGACT (p.T7FfsX7; 1/22). All of these seventeen cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions: The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in our country and it could be the basis for future genetic counseling in Portuguese population.
publishDate 2018
dc.date.none.fl_str_mv 2018-12-28
2018-12-28T00:00:00Z
2019-03-25T17:29:16Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/6305
url http://hdl.handle.net/10400.18/6305
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Open J Genet. 2018;8(4):91-100. doi:10.4236/ojgen.2018.84008
2162-4453
10.4236/ojgen.2018.84008
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Scientific Research Publishing
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dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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