title: Extracellular matrix and nuclear abnormalities in skeletal muscle of a patient with Walker-Warburg syndrome caused by POMT1 mutation.
abstract: Walker-Warburg syndrome (WWS) is an autosomal recessive disorder characterized by congenital muscular dystrophy, structural eye abnormalities and severe brain malformations. We performed an immunohistochemical and electron microscopy study of a muscle biopsy from a patient affected by WWS carrying a homozygous frameshift mutation in O-mannosyltransferase 1 gene (POMT1). alpha-Dystroglycan glycosylated epitope was not detected in muscle fibers and intramuscular peripheral nerves. Laminin alpha2 chain and perlecan were reduced in muscle fibers and well preserved in intramuscular peripheral nerves. The basal lamina in several muscle fibers showed discontinuities and detachment from the plasmalemma. Most nuclei, including myonuclei and satellite cell nuclei, showed detachment or complete absence of peripheral heterochromatin from the nuclear envelope. Apoptotic changes were detected in 3% of muscle fibers. The particular combination of basal lamina and nuclear changes may suggest that a complex pathogenetic mechanism, affecting several subcellular compartments, underlies the degenerative process in WWS muscle.
authors.affiliation: Istituto per i Trapianti d'organo e l'Immunocitologia (ITOI) CNR, c/o IOR, Bologna, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Sabatelli
authors.forename: Marta
authors.initials: M
authors.lastname: Columbaro
authors.forename: Isabella
authors.initials: I
authors.lastname: Mura
authors.forename: Cristina
authors.initials: C
authors.lastname: Capanni
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lattanzi
authors.forename: Nadir M
authors.initials: NM
authors.lastname: Maraldi
authors.forename: Daniel
authors.initials: D
authors.lastname: Beltràn-Valero de Barnabè
authors.forename: Hans
authors.initials: H
authors.lastname: van Bokoven
authors.forename: Stefano
authors.initials: S
authors.lastname: Squarzoni
authors.forename: Luciano
authors.initials: L
authors.lastname: Merlini
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D001921:Brain / Q000002:abnormalities; D002467:Cell Nucleus / Q000648:ultrastructure; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000378:metabolism; D049030:Dystroglycans; D005109:Extracellular Matrix / Q000648:ultrastructure; D005124:Eye Abnormalities / Q000201:enzymology / Q000235:genetics; D016368:Frameshift Mutation; D005808:Genes, Recessive; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008297:Male; D008364:Mannosyltransferases / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism / Q000648:ultrastructure*; D009136:Muscular Dystrophies / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D013577:Syndrome
chemical_list: D015703:Antigens, CD; D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D019812:Heparan Sulfate Proteoglycans; D039001:Integrin alpha Chains; D007797:Laminin; D008562:Membrane Glycoproteins; C085725:integrin alpha7; C102645:laminin alpha 2; C071927:perlecan; D049030:Dystroglycans; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase