Extracellular matrix and nuclear abnormalities in skeletal muscle of a patient with Walker-Warburg syndrome caused by POMT1 mutation

Patrizia Sabatelli, Marta Columbaro, Isabella Mura, Cristina Capanni, Giovanna Lattanzi, Nadir M. Maraldi, Daniel Beltràn-Valero De Barnabè, Hans Van Bokoven, Stefano Squarzoni, Luciano Merlini

Research output: Contribution to journalArticle


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). α-Dystroglycan glycosylated epitope was not detected in muscle fibers and intramuscular peripheral nerves. Laminin α2 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.

Original languageEnglish
Pages (from-to)57-62
Number of pages6
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number1
Publication statusPublished - May 20 2003



  • α-Dystroglycan
  • Basal lamina
  • Chromatin
  • Glycosylation
  • Walker-Warburg syndrome

ASJC Scopus subject areas

  • Biophysics
  • Molecular Biology
  • Molecular Medicine

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