Genotype-Phenotype Correlations in PMM2-CDG
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/10400.16/2841 |
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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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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1799133657981517824 |