GM1 gangliosidosis and Morquio B disease: An update on genetic alterations and clinical findings

Anna Caciotti, Scott C. Garman, Yadilette Rivera-Colón, Elena Procopio, Serena Catarzi, Lorenzo Ferri, Carmen Guido, Paola Martelli, Rossella Parini, Daniela Antuzzi, Roberta Battini, Michela Sibilio, Alessandro Simonati, Elena Fontana, Alessandro Salviati, Gulcin Akinci, Cristina Cereda, Carlo Dionisi-Vici, Francesca Deodato, Adele d'AmicoAlessandra d'Azzo, Enrico Bertini, Mirella Filocamo, Maurizio Scarpa, Maja di Rocco, Cynthia J. Tifft, Federica Ciani, Serena Gasperini, Elisabetta Pasquini, Renzo Guerrini, Maria Alice Donati, Amelia Morrone

Research output: Contribution to journalArticlepeer-review


GM1 gangliosidosis and Morquio B syndrome, both arising from beta-galactosidase (GLB1) deficiency, are very rare lysosomal storage diseases with an incidence of about 1:100,000-1:200,000 live births worldwide. Here we report the beta-galactosidase gene (GLB1) mutation analysis of 21 unrelated GM1 gangliosidosis patients, and of 4 Morquio B patients, of whom two are brothers. Clinical features of the patients were collected and compared with those in literature. In silico analyses were performed by standard alignments tools and by an improved version of GLB1 three-dimensional models. The analysed cohort includes remarkable cases. One patient with GM1 gangliosidosis had a triple X syndrome. One patient with juvenile GM1 gangliosidosis was homozygous for a mutation previously identified in Morquio type B. A patient with infantile GM1 gangliosidosis carried a complex GLB1 allele harbouring two genetic variants leading to p.R68W and p.R109W amino acid changes, in trans with the known p.R148C mutation. Molecular analysis showed 27 mutations, 9 of which are new: 5 missense, 3 microdeletions and a nonsense mutation. We also identified four new genetic variants with a predicted polymorphic nature that was further investigated by in silico analyses. Three-dimensional structural analysis of GLB1 homology models including the new missense mutations and the p.R68W and p.R109W amino acid changes showed that all the amino acid replacements affected the resulting protein structures in different ways, from changes in polarity to folding alterations. Genetic and clinical associations led us to undertake a critical review of the classifications of late-onset GM1 gangliosidosis and Morquio B disease.

Original languageEnglish
Pages (from-to)782-790
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number7
Publication statusPublished - Jul 2011


  • Beta-galactosidase
  • GM1 gangliosidosis
  • Homology modelling
  • Morquio B
  • Mutation update

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

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