Congenital Disorders of Glycosylation in Portugal—Two Decades of Experience
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.17/4292 |
Resumo: | Objective: To describe the clinical, biochemical, and genetic features of both new and previously reported patients with congenital disorders of glycosylation (CDGs) diagnosed in Portugal over the last 20 years. Study design: The cohort includes patients with an unexplained multisystem or single organ involvement, with or without psychomotor disability. Serum sialotransferrin isoforms and, whenever necessary, apolipoprotein CIII isoforms and glycan structures were analyzed. Additional studies included measurement of phosphomannomutase (PMM) activity and analysis of lipid-linked oligosaccharides in fibroblasts. Sanger sequencing and massive parallel sequencing were used to identify causal variants or the affected gene, respectively. Results: Sixty-three individuals were diagnosed covering 14 distinct CDGs; 43 patients diagnosed postnatally revealed a type 1, 14 a type 2, and 2 a normal pattern on serum transferrin isoelectrofocusing. The latter patients were identified by whole exome sequencing. Nine of them presented also a hypoglycosylation pattern on apolipoprotein CIII isoelectrofocusing, pointing to an associated O-glycosylation defect. Most of the patients (62%) are PMM2-CDG and the remaining carry pathogenic variants in ALG1, ATP6AP1, ATP6AP2, ATP6V0A2, CCDC115, COG1, COG4, DPAGT1, MAN1B1, SLC35A2, SRD5A3, RFT1, or PGM1. Conclusions: Portuguese patients with CDGs are presented in this report, some of them showing unique clinical phenotypes. Among the 14 genes mutated in Portuguese individuals, 8 are shared with a previously reported Spanish cohort. However, regarding the mutational spectrum of PMM2-CDG, the most frequent CDG, a striking similarity between the 2 populations was found, as only 1 mutated allele found in the Portuguese group has not been reported in Spain. |
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Congenital Disorders of Glycosylation in Portugal—Two Decades of ExperienceCDGPMM2 genotypeCongenital disorder/glycosylationPhenotypeTransferrinHDE MTBObjective: To describe the clinical, biochemical, and genetic features of both new and previously reported patients with congenital disorders of glycosylation (CDGs) diagnosed in Portugal over the last 20 years. Study design: The cohort includes patients with an unexplained multisystem or single organ involvement, with or without psychomotor disability. Serum sialotransferrin isoforms and, whenever necessary, apolipoprotein CIII isoforms and glycan structures were analyzed. Additional studies included measurement of phosphomannomutase (PMM) activity and analysis of lipid-linked oligosaccharides in fibroblasts. Sanger sequencing and massive parallel sequencing were used to identify causal variants or the affected gene, respectively. Results: Sixty-three individuals were diagnosed covering 14 distinct CDGs; 43 patients diagnosed postnatally revealed a type 1, 14 a type 2, and 2 a normal pattern on serum transferrin isoelectrofocusing. The latter patients were identified by whole exome sequencing. Nine of them presented also a hypoglycosylation pattern on apolipoprotein CIII isoelectrofocusing, pointing to an associated O-glycosylation defect. Most of the patients (62%) are PMM2-CDG and the remaining carry pathogenic variants in ALG1, ATP6AP1, ATP6AP2, ATP6V0A2, CCDC115, COG1, COG4, DPAGT1, MAN1B1, SLC35A2, SRD5A3, RFT1, or PGM1. Conclusions: Portuguese patients with CDGs are presented in this report, some of them showing unique clinical phenotypes. Among the 14 genes mutated in Portuguese individuals, 8 are shared with a previously reported Spanish cohort. However, regarding the mutational spectrum of PMM2-CDG, the most frequent CDG, a striking similarity between the 2 populations was found, as only 1 mutated allele found in the Portuguese group has not been reported in Spain.ElsevierRepositório do Centro Hospitalar Universitário de Lisboa Central, EPEQuelhas, DMartins, EAzevedo, LBandeira, ADiogo, LGarcia, PSequeira, SFerreira, ACTeles, ELRodrigues, EFortuna, AMMendonça, CFernandes, HCMedeira, AGaspar, AJaneiro, POliveira, ALaranjeira, FRibeiro, ISouche, ERace, VKeldermans, LMatthijs, GJaeken, J2022-11-24T16:12:43Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.17/4292engJ Pediatr . 2021 Apr;231:148-156.10.1016/j.jpeds.2020.12.026info: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:RCAAP2024-10-28T10:30:32Zoai:repositorio.chlc.pt:10400.17/4292Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-10-28T10:30:32Repositório 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 |
Congenital Disorders of Glycosylation in Portugal—Two Decades of Experience |
title |
Congenital Disorders of Glycosylation in Portugal—Two Decades of Experience |
spellingShingle |
Congenital Disorders of Glycosylation in Portugal—Two Decades of Experience Quelhas, D CDG PMM2 genotype Congenital disorder/glycosylation Phenotype Transferrin HDE MTB |
title_short |
Congenital Disorders of Glycosylation in Portugal—Two Decades of Experience |
title_full |
Congenital Disorders of Glycosylation in Portugal—Two Decades of Experience |
title_fullStr |
Congenital Disorders of Glycosylation in Portugal—Two Decades of Experience |
title_full_unstemmed |
Congenital Disorders of Glycosylation in Portugal—Two Decades of Experience |
title_sort |
Congenital Disorders of Glycosylation in Portugal—Two Decades of Experience |
author |
Quelhas, D |
author_facet |
Quelhas, D Martins, E Azevedo, L Bandeira, A Diogo, L Garcia, P Sequeira, S Ferreira, AC Teles, EL Rodrigues, E Fortuna, AM Mendonça, C Fernandes, HC Medeira, A Gaspar, A Janeiro, P Oliveira, A Laranjeira, F Ribeiro, I Souche, E Race, V Keldermans, L Matthijs, G Jaeken, J |
author_role |
author |
author2 |
Martins, E Azevedo, L Bandeira, A Diogo, L Garcia, P Sequeira, S Ferreira, AC Teles, EL Rodrigues, E Fortuna, AM Mendonça, C Fernandes, HC Medeira, A Gaspar, A Janeiro, P Oliveira, A Laranjeira, F Ribeiro, I Souche, E Race, V Keldermans, L Matthijs, G Jaeken, J |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório do Centro Hospitalar Universitário de Lisboa Central, EPE |
dc.contributor.author.fl_str_mv |
Quelhas, D Martins, E Azevedo, L Bandeira, A Diogo, L Garcia, P Sequeira, S Ferreira, AC Teles, EL Rodrigues, E Fortuna, AM Mendonça, C Fernandes, HC Medeira, A Gaspar, A Janeiro, P Oliveira, A Laranjeira, F Ribeiro, I Souche, E Race, V Keldermans, L Matthijs, G Jaeken, J |
dc.subject.por.fl_str_mv |
CDG PMM2 genotype Congenital disorder/glycosylation Phenotype Transferrin HDE MTB |
topic |
CDG PMM2 genotype Congenital disorder/glycosylation Phenotype Transferrin HDE MTB |
description |
Objective: To describe the clinical, biochemical, and genetic features of both new and previously reported patients with congenital disorders of glycosylation (CDGs) diagnosed in Portugal over the last 20 years. Study design: The cohort includes patients with an unexplained multisystem or single organ involvement, with or without psychomotor disability. Serum sialotransferrin isoforms and, whenever necessary, apolipoprotein CIII isoforms and glycan structures were analyzed. Additional studies included measurement of phosphomannomutase (PMM) activity and analysis of lipid-linked oligosaccharides in fibroblasts. Sanger sequencing and massive parallel sequencing were used to identify causal variants or the affected gene, respectively. Results: Sixty-three individuals were diagnosed covering 14 distinct CDGs; 43 patients diagnosed postnatally revealed a type 1, 14 a type 2, and 2 a normal pattern on serum transferrin isoelectrofocusing. The latter patients were identified by whole exome sequencing. Nine of them presented also a hypoglycosylation pattern on apolipoprotein CIII isoelectrofocusing, pointing to an associated O-glycosylation defect. Most of the patients (62%) are PMM2-CDG and the remaining carry pathogenic variants in ALG1, ATP6AP1, ATP6AP2, ATP6V0A2, CCDC115, COG1, COG4, DPAGT1, MAN1B1, SLC35A2, SRD5A3, RFT1, or PGM1. Conclusions: Portuguese patients with CDGs are presented in this report, some of them showing unique clinical phenotypes. Among the 14 genes mutated in Portuguese individuals, 8 are shared with a previously reported Spanish cohort. However, regarding the mutational spectrum of PMM2-CDG, the most frequent CDG, a striking similarity between the 2 populations was found, as only 1 mutated allele found in the Portuguese group has not been reported in Spain. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021 2021-01-01T00:00:00Z 2022-11-24T16:12:43Z |
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/10400.17/4292 |
url |
http://hdl.handle.net/10400.17/4292 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
J Pediatr . 2021 Apr;231:148-156. 10.1016/j.jpeds.2020.12.026 |
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 |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
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 |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
mluisa.alvim@gmail.com |
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1817548658265030656 |