ArticleJournal of inherited metabolic disease2011
Expression analysis revealing destabilizing mutations in phosphomannomutase 2 deficiency (PMM2-CDG): expression analysis of PMM2-CDG mutations.
Article in Journal of inherited metabolic disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
- A comprehensive update of genotype-phenotype correlations in PMM2-CDG: insights from molecular and structural analyses.Orphanet journal of rare diseases · 2025Review
- Congenital disorder of glycosylation type Ia in a Chinese family: Function analysis of a novelMolecular genetics and metabolism reports · 2024Article
- Instrumented assessment of gait disturbance in PMM2-CDG adults: a feasibility analysis.Orphanet journal of rare diseases · 2024Article
- Genotype/Phenotype Relationship: Lessons From 137 Patients With PMM2-CDG.Human mutation · 2024Observational
- Cysteine Pathogenic Variants of PMM2 Are Sensitive to Environmental Stress with Loss of Structural Stability.Oxidative medicine and cellular longevity · 2023Article
- Evaluation of Cell Models to Study Monocyte Functions in PMM2 Congenital Disorders of Glycosylation.Frontiers in immunology · 2022Article
- Genotype-Phenotype Correlations in PMM2-CDG.Genes · 2021Article
- Clinical and radiological correlates of activities of daily living in cerebellar atrophy caused by PMM2 mutations (PMM2-CDG).Cerebellum (London, England) · 2021Article
- Cystic kidney diseases associated with mutations in phosphomannomutase 2 promotor: a large spectrum of phenotypes.Pediatric nephrology (Berlin, Germany) · 2021Article
- Congenital disorders of glycosylation: Prevalence, incidence and mutational spectrum in the Polish population.Molecular genetics and metabolism reports · 2021Article
- Vascular ring anomaly in a patient with phosphomannomutase 2 deficiency: A case report and review of the literature.JIMD reports · 2020Article
- Article
- β-Glucose-1,6-Bisphosphate Stabilizes Pathological Phophomannomutase2 Mutants In Vitro and Represents a Lead Compound to Develop Pharmacological Chaperones for the Most Common Disorder of Glycosylation, PMM2-CDG.International journal of molecular sciences · 2019Article
- Yeast Models of Phosphomannomutase 2 Deficiency, a Congenital Disorder of Glycosylation.G3 (Bethesda, Md.) · 2019Article
- The Analysis of Variants in the General Population Reveals ThatInternational journal of molecular sciences · 2018Article
- CDG Therapies: From Bench to Bedside.International journal of molecular sciences · 2018Review
- Genetic predisposition to fetal alcohol syndrome: association with congenital disorders of N-glycosylation.Pediatric research · 2018Article
- Clinical exome sequencing for cerebellar ataxia and spastic paraplegia uncovers novel gene-disease associations and unanticipated rare disorders.European journal of human genetics : EJHG · 2016Article
- Phosphomannomutase deficiency (PMM2-CDG): ataxia and cerebellar assessment.Orphanet journal of rare diseases · 2015Article
- A nationwide survey of PMM2-CDG in Italy: high frequency of a mild neurological variant associated with the L32R mutation.Journal of neurology · 2015Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deficiency of phosphomannomutase (PMM2, MIM#601785) is the most common congenital disorder of glycosylation. Herein we report the genetic analysis of 22 Spanish PMM2 deficient patients and the functional analysis of 14 nucleotide changes in a prokaryotic expression system in order to elucidate their molecular pathogenesis. PMM2 activity assay revealed the presence of six protein changes with no enzymatic activities (p.R123Q, p.R141H, p.F157S, p.P184T, p.F207S and p.D209G) and seven mild protein changes with residual activities ranging from 16 to 54% (p.L32R, p.V44A p.D65Y, p.P113L p.T118S, p.T237M and p.C241S) and also one variant change with normal activity (p.E197A). The results obtained from Western blot analysis, degradation time courses of 11 protein changes and structural analysis of the PMM2 protein, suggest that the loss-of-function of most mutant proteins is based on their increased susceptibility to degradation or aggregation compared to the wild type protein, considering PMM2 deficiency as a conformational disease. We have identified exclusively catalytic protein change (p.D209G), catalytic protein changes affecting protein stability (p.R123Q and p.R141H), two protein changes disrupting the dimer interface (p.P113L and p.T118S) and several misfolding changes (p.L32R, p.V44A, p.D65Y, p.F157S, p.P184T, p.F207S, p.T237M and p.C241S). Our current work opens a promising therapeutic option using pharmacological chaperones to revert the effect of the characterized misfolding mutations identified in a wide range of PMM2 deficient patients.
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