title: Protein O-mannosyltransferase activities in lymphoblasts from patients with alpha-dystroglycanopathies.
abstract: Defects in O-mannosylation of alpha-dystroglycan cause some forms of congenital muscular dystrophy (CMD), the so-called alpha-dystroglycanopathies. Six genes are responsible for these diseases with overlapping phenotypes. We investigated the usefulness of a biochemical approach for the diagnosis and investigation of the alpha-dystroglycanopathies using immortalized lymphoblasts prepared from genetically diagnosed and undiagnosed CMD patients and from control subjects. We measured the activities of protein O-mannose beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) and protein O-mannosyltransferase (POMT). Lymphoblasts from patients harbouring known mutations in either POMGNT1 or POMT1 showed a marked decrease in POMGnT1 or POMT activity, respectively, compared to controls. Furthermore, we identified pathogenic mutations in POMGNT1, POMT1 or POMT2 in six previously genetically uncharacterised patients who had very low enzyme activity. In conclusion, the lymphoblast-based enzymatic assay is a sensitive and useful method (i) to select patients harbouring POMGNT1, POMT1 or POMT2 mutations; (ii) to assess the pathogenicity of new or already described mutations.
authors.affiliation: Glycobiology Research Group, Tokyo Metropolitan Institute of Gerontology, Foundation for Research on Aging and Promotion of Human Welfare, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Manya
authors.forename: Céline
authors.initials: C
authors.lastname: Bouchet
authors.forename: Akiko
authors.initials: A
authors.lastname: Yanagisawa
authors.forename: Sandrine
authors.initials: S
authors.lastname: Vuillaumier-Barrot
authors.forename: Susana
authors.initials: S
authors.lastname: Quijano-Roy
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Svetlana
authors.initials: S
authors.lastname: Maugenre
authors.forename: Pascale
authors.initials: P
authors.lastname: Richard
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Inazu
authors.forename: Luciano
authors.initials: L
authors.lastname: Merlini
authors.forename: Norma B
authors.initials: NB
authors.lastname: Romero
authors.forename: France
authors.initials: F
authors.lastname: Leturcq
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bezier
authors.forename: Haluk
authors.initials: H
authors.lastname: Topaloglu
authors.forename: Brigitte
authors.initials: B
authors.lastname: Estournet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Seta
authors.forename: Tamao
authors.initials: T
authors.lastname: Endo
authors.forename: Pascale
authors.initials: P
authors.lastname: Guicheney
mesh_terms: D001681:Biological Assay / Q000379:methods; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D015536:Down-Regulation / Q000235:genetics; D049030:Dystroglycans / Q000235:genetics*; D004789:Enzyme Activation / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005820:Genetic Testing; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000201:enzymology; D008364:Mannosyltransferases / Q000235:genetics*; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D011237:Predictive Value of Tests
chemical_list: C483081:DAG1 protein, human; D005819:Genetic Markers; D007527:Isoenzymes; D049030:Dystroglycans; D008364:Mannosyltransferases; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase; C082696:protein O-mannosyltransferase