DPM2-CDG: A muscular dystrophy-dystroglycanopathy syndrome with severe epilepsy

Autor: Barone, RITA MARIA ELISA, Aiello, C, Race, V, Morava, E, Foulquier, F, Riemersma, M, Passarelli, C, Concolino, D, Carella, M, Santorelli, F, Vleugels, W, Mercuri, E, Garozzo, Domenico, Sturiale, L, Messina, S, Jaeken, J, Fiumara, Agata, Wevers, Ra, Bertini, E, Matthijs, G, 2012 Oct, Lefeber D. J. Ann N. e. u. r. o. l., 72:550, 8.
Rok vydání: 2012
Předmět:
Male
Glycosylation
DNA Mutational Analysis
Drug Resistance
Endoplasmic Reticulum
medicine.disease_cause
Compound heterozygosity
Mannosyltransferases
Muscular Dystrophies
chemistry.chemical_compound
Congenital Disorders of Glycosylation
Pregnancy
Missense mutation
Muscular dystrophy
Child
Dystroglycans
Mutation
Liver Diseases
Middle Aged
Hypotonia
Neurology
Child
Preschool
Microcephaly
Female
medicine.symptom
Lipid glycosylation
Adult
medicine.medical_specialty
Adolescent
Molecular Sequence Data
Mutation
Missense
Vision Disorders
DOLICHOL-PHOSPHATE-MANNOSE
CAUSES CONGENITAL DISORDER
MAMMALIAN-CELLS
GLYCOSYLATION
SYNTHASE
BIOSYNTHESIS
GENE
DPM1
PROTEIN
IE
Coagulation Protein Disorders
Biology
Genomic disorders and inherited multi-system disorders [IGMD 3]
Young Adult
Internal medicine
medicine
Humans
Glycostation disorders [DCN PAC - Perception action and control IGMD 4]
DCN NN - Brain networks and neuronal communication
Aged
Epilepsy
Electromyography
Endoplasmic reticulum
Infant
Glycostation disorders [IGMD 4]
Fibroblasts
medicine.disease
Genetics and epigenetic pathways of disease DCN MP - Plasticity and memory [NCMLS 6]
Endocrinology
chemistry
Neurology (clinical)
Isoelectric Focusing
Mannose
Zdroj: Annals of Neurology, 72, 550-8
Annals of neurology 72 (2012): 550–558. doi:10.1002/ana.23632
info:cnr-pdr/source/autori:R.Barone, Ch.Aiello, V.Race, E.Morava, F.Foulquier, M.Riemersma, Ch.Passarelli, D.Concolino, M.Carella, F.Santorelli, W.Vleugels, E.Mercuri, D.Garozzo, L.Sturiale, S.Messina, J.Jaeken, A.Fiumara, R.A.Wevers, E.Bertini, G.Matthijs, D. J.Lefeber/titolo:DPM2-CDG: A Muscular Dystrophy-Dystroglycanopathy Syndrome with Severe Epilepsy/doi:10.1002%2Fana.23632/rivista:Annals of neurology/anno:2012/pagina_da:550/pagina_a:558/intervallo_pagine:550–558/volume:72
Annals of Neurology, 72, 4, pp. 550-8
ISSN: 0364-5134
Popis: Item does not contain fulltext OBJECTIVE: Congenital disorders of glycosylation (CDG) are a group of metabolic diseases due to defects in protein and lipid glycosylation. We searched for the primary defect in 3 children from 2 families with a severe neurological phenotype, including profound developmental delay, intractable epilepsy, progressive microcephaly, severe hypotonia with elevated blood creatine kinase levels, and early fatal outcome. There was clinical evidence of a muscular dystrophy-dystroglycanopathy syndrome, supported by deficient O-mannosylation by muscle immunohistochemistry. METHODS: Biochemical and molecular methods were combined to pinpoint the defect in the glycosylation pathway in the endoplasmic reticulum. RESULTS: Metabolic investigations revealed CDG-I, pointing to a defect in protein N-glycosylation in the endoplasmic reticulum. Analysis of lipid-linked oligosaccharides in fibroblasts showed accumulation of Dol-PP-GlcNAc(2) -Man(5) . DNA analysis revealed mutations in DPM2, 1 of the subunits of the dolichol-phosphate-mannose (DPM) synthase; the patient in the first family is compound heterozygous for 2 mutations (c.68A>G, predicting a missense mutation p.Y23C and c.4-1G>C, a splice mutation), whereas the patients in the second family are homozygous for the same missense mutation (c.68A>G, p.Y23C). INTERPRETATION: We describe a new CDG, due to a deficiency of DPM2. Hence, mutations have now been described in the genes for the 3 subunits of DPM: DPM1, DPM2, and DPM3, whereby DPM2-CDG links the congenital disorders of glycosylation to the congenital muscular dystrophies. ANN NEUROL 2012;72:550-558.
Databáze: OpenAIRE
Externí odkaz: