Genotype-Phenotype Correlations in PMM2-CDG

Detalhes bibliográficos
Autor(a) principal: Vaes, Laurien
Data de Publicação: 2021
Outros Autores: Rymen, Daisy, Cassiman, David, Ligezka, Anna, Vanhoutvin, Nele, Quelhas, D, Morava, Eva, Witters, Peter
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.16/2841
Resumo: PMM2-CDG is a rare disease, causing hypoglycosylation of multiple proteins, hence preventing full functionality. So far, no direct genotype-phenotype correlations have been identified. We carried out a retrospective cohort study on 26 PMM2-CDG patients. We collected the identified genotype, as well as continuous variables indicating the disease severity (based on Nijmegen Pediatric CDG Rating Score or NPCRS) and dichotomous variables reflecting the patients' phenotype. The phenotypic effects of patients' genotype were studied using non-parametric and Chi-Square tests. Seventeen different pathogenic variants have been studied. Variants with zero enzyme activity had no significant impact on the Nijmegen score. Pathogenic variants involving the stabilization/folding domain have a significantly lower total NPCRS (p = 0.017): presence of the p.Cys241Ser mutation had a significantly lower subscore 1,3 and NPCRS (p = 0.04) and thus result in a less severe phenotype. On the other hand, variants involving the dimerization domain, p.Pro113Leu and p.Phe119Leu, resulted in a significantly higher NPCRS score (p = 0.002), which indicates a worse clinical course. These concepts give a better insight in the phenotypic prognosis of PMM2-CDG, according to their molecular base.
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spelling Genotype-Phenotype Correlations in PMM2-CDGNPCRSPMM2-CDGcongenital disorders of glycosylationgenotypemutationPMM2-CDG is a rare disease, causing hypoglycosylation of multiple proteins, hence preventing full functionality. So far, no direct genotype-phenotype correlations have been identified. We carried out a retrospective cohort study on 26 PMM2-CDG patients. We collected the identified genotype, as well as continuous variables indicating the disease severity (based on Nijmegen Pediatric CDG Rating Score or NPCRS) and dichotomous variables reflecting the patients' phenotype. The phenotypic effects of patients' genotype were studied using non-parametric and Chi-Square tests. Seventeen different pathogenic variants have been studied. Variants with zero enzyme activity had no significant impact on the Nijmegen score. Pathogenic variants involving the stabilization/folding domain have a significantly lower total NPCRS (p = 0.017): presence of the p.Cys241Ser mutation had a significantly lower subscore 1,3 and NPCRS (p = 0.04) and thus result in a less severe phenotype. On the other hand, variants involving the dimerization domain, p.Pro113Leu and p.Phe119Leu, resulted in a significantly higher NPCRS score (p = 0.002), which indicates a worse clinical course. These concepts give a better insight in the phenotypic prognosis of PMM2-CDG, according to their molecular base.E.M. was funded by the grant titled Frontiers in Congenital Disorders of Glycosylation(1U54NS115198-01) from the National Institute of Neurological Diseases and Stroke (NINDS)and the National Center for Advancing Translational Sciences (NCATS), at the National Institute of Health. P.W. was funded by the Fonds Wetenschappelijk Onderzoek-Vlaanderen (Fundamenteel Klinisch Mandaat 18B4322N)MDPIRepositório Científico do Centro Hospitalar Universitário de Santo AntónioVaes, LaurienRymen, DaisyCassiman, DavidLigezka, AnnaVanhoutvin, NeleQuelhas, DMorava, EvaWitters, Peter2023-10-24T09:38:57Z2021-102021-10-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.16/2841engVaes L, Rymen D, Cassiman D, et al. Genotype-Phenotype Correlations in PMM2-CDG. Genes (Basel). 2021;12(11):1658. doi:10.3390/genes121116582073-442510.3390/genes12111658info: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:RCAAP2023-10-26T05:19:17Zoai:repositorio.chporto.pt:10400.16/2841Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:39:38.843182Repositório 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 Genotype-Phenotype Correlations in PMM2-CDG
title Genotype-Phenotype Correlations in PMM2-CDG
spellingShingle Genotype-Phenotype Correlations in PMM2-CDG
Vaes, Laurien
NPCRS
PMM2-CDG
congenital disorders of glycosylation
genotype
mutation
title_short Genotype-Phenotype Correlations in PMM2-CDG
title_full Genotype-Phenotype Correlations in PMM2-CDG
title_fullStr Genotype-Phenotype Correlations in PMM2-CDG
title_full_unstemmed Genotype-Phenotype Correlations in PMM2-CDG
title_sort Genotype-Phenotype Correlations in PMM2-CDG
author Vaes, Laurien
author_facet Vaes, Laurien
Rymen, Daisy
Cassiman, David
Ligezka, Anna
Vanhoutvin, Nele
Quelhas, D
Morava, Eva
Witters, Peter
author_role author
author2 Rymen, Daisy
Cassiman, David
Ligezka, Anna
Vanhoutvin, Nele
Quelhas, D
Morava, Eva
Witters, Peter
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Centro Hospitalar Universitário de Santo António
dc.contributor.author.fl_str_mv Vaes, Laurien
Rymen, Daisy
Cassiman, David
Ligezka, Anna
Vanhoutvin, Nele
Quelhas, D
Morava, Eva
Witters, Peter
dc.subject.por.fl_str_mv NPCRS
PMM2-CDG
congenital disorders of glycosylation
genotype
mutation
topic NPCRS
PMM2-CDG
congenital disorders of glycosylation
genotype
mutation
description PMM2-CDG is a rare disease, causing hypoglycosylation of multiple proteins, hence preventing full functionality. So far, no direct genotype-phenotype correlations have been identified. We carried out a retrospective cohort study on 26 PMM2-CDG patients. We collected the identified genotype, as well as continuous variables indicating the disease severity (based on Nijmegen Pediatric CDG Rating Score or NPCRS) and dichotomous variables reflecting the patients' phenotype. The phenotypic effects of patients' genotype were studied using non-parametric and Chi-Square tests. Seventeen different pathogenic variants have been studied. Variants with zero enzyme activity had no significant impact on the Nijmegen score. Pathogenic variants involving the stabilization/folding domain have a significantly lower total NPCRS (p = 0.017): presence of the p.Cys241Ser mutation had a significantly lower subscore 1,3 and NPCRS (p = 0.04) and thus result in a less severe phenotype. On the other hand, variants involving the dimerization domain, p.Pro113Leu and p.Phe119Leu, resulted in a significantly higher NPCRS score (p = 0.002), which indicates a worse clinical course. These concepts give a better insight in the phenotypic prognosis of PMM2-CDG, according to their molecular base.
publishDate 2021
dc.date.none.fl_str_mv 2021-10
2021-10-01T00:00:00Z
2023-10-24T09:38:57Z
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/10400.16/2841
url http://hdl.handle.net/10400.16/2841
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Vaes L, Rymen D, Cassiman D, et al. Genotype-Phenotype Correlations in PMM2-CDG. Genes (Basel). 2021;12(11):1658. doi:10.3390/genes12111658
2073-4425
10.3390/genes12111658
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 MDPI
publisher.none.fl_str_mv MDPI
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
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