Genotype-Phenotype Correlations in PMM2-CDG

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...

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Autores principales:	Laurien Vaes, Daisy Rymen, David Cassiman, Anna Ligezka, Nele Vanhoutvin, Dulce Quelhas, Eva Morava, Peter Witters
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	PMM2-CDG NPCRS congenital disorders of glycosylation genotype mutation Genetics QH426-470
Acceso en línea:	https://doaj.org/article/fa5a42e1e7824189a707a7573818f6a6
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spelling	oai:doaj.org-article:fa5a42e1e7824189a707a7573818f6a62021-11-25T17:40:19ZGenotype-Phenotype Correlations in PMM2-CDG10.3390/genes121116582073-4425https://doaj.org/article/fa5a42e1e7824189a707a7573818f6a62021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1658https://doaj.org/toc/2073-4425PMM2-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 (<i>p</i> = 0.017): presence of the p.Cys241Ser mutation had a significantly lower subscore 1,3 and NPCRS (<i>p</i> = 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 (<i>p</i> = 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.Laurien VaesDaisy RymenDavid CassimanAnna LigezkaNele VanhoutvinDulce QuelhasEva MoravaPeter WittersMDPI AGarticlePMM2-CDGNPCRScongenital disorders of glycosylationgenotypemutationGeneticsQH426-470ENGenes, Vol 12, Iss 1658, p 1658 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PMM2-CDG NPCRS congenital disorders of glycosylation genotype mutation Genetics QH426-470
spellingShingle	PMM2-CDG NPCRS congenital disorders of glycosylation genotype mutation Genetics QH426-470 Laurien Vaes Daisy Rymen David Cassiman Anna Ligezka Nele Vanhoutvin Dulce Quelhas Eva Morava Peter Witters Genotype-Phenotype Correlations in PMM2-CDG
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 (<i>p</i> = 0.017): presence of the p.Cys241Ser mutation had a significantly lower subscore 1,3 and NPCRS (<i>p</i> = 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 (<i>p</i> = 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.
format	article
author	Laurien Vaes Daisy Rymen David Cassiman Anna Ligezka Nele Vanhoutvin Dulce Quelhas Eva Morava Peter Witters
author_facet	Laurien Vaes Daisy Rymen David Cassiman Anna Ligezka Nele Vanhoutvin Dulce Quelhas Eva Morava Peter Witters
author_sort	Laurien Vaes
title	Genotype-Phenotype Correlations in PMM2-CDG
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
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/fa5a42e1e7824189a707a7573818f6a6
work_keys_str_mv	AT laurienvaes genotypephenotypecorrelationsinpmm2cdg AT daisyrymen genotypephenotypecorrelationsinpmm2cdg AT davidcassiman genotypephenotypecorrelationsinpmm2cdg AT annaligezka genotypephenotypecorrelationsinpmm2cdg AT nelevanhoutvin genotypephenotypecorrelationsinpmm2cdg AT dulcequelhas genotypephenotypecorrelationsinpmm2cdg AT evamorava genotypephenotypecorrelationsinpmm2cdg AT peterwitters genotypephenotypecorrelationsinpmm2cdg
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Genotype-Phenotype Correlations in PMM2-CDG

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