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- Title
OTHER LYSOSOMAL STORAGE DISEASES.
- Authors
Caciotti, A.; Donati, M. A.; Pasquini, E.; Carraresi, L.; D'Azzo, A.; Dionisi Vici, C.; Di Rocco, M.; Parini, R.; Antuzzi, D.; Zammarchi, E.; Guerrini, R.; Morrone, A.
- Abstract
A Caciotti1, MA Donati1, E Pasquini1, L Carraresi1, A D'Azzo2, C Dionisi Vici3, M Di Rocco4, R Parini5, D Antuzzi6, E Zammarchi1, R Guerrini1, A Morrone1 1. Metabolic and Muscular Unit, Clinic of Pediatric Neurology, AOU Meyer, Florence, Italy 2. Department of Genetics, St. Jude Children's Research Hospital, Memphis, TN, USA 3. Ospedale Bambin Gesù, Rome, Italy 4. II Pediatric Unit, Istituto Gaslini, Genoa, Italy 5. II Clinical Paediatrics, Milan, Italy 6. Catholic University, Rome, Italy Aim: Deficiency of the lysosomal hydrolase β-galactosidase (GLB1; encoded by the GLB1 gene) causes GM1 gangliosidosis, a rare autosomal recessive disease (incidence approximately 1:100 000 births). We report on a broad range of clinical symptoms and molecular findings with the aim of clarifying the characterization of the phenotype/genotype variability in this disorder. Patients: Within the past 10 years, our unit has collected data from 34 patients worldwide with the infantile, juvenile and adult forms of GM1 gangliosidosis. Results: In the late infantile form of GM1 gangliosidosis, which was the most frequent form in this group of patients (with or without cardiomyopathy), the p.L436F amino acid change was found to act as a non-benign polymorphism affecting the molecular basis of the GLB1 gene. Indeed, Western blot analysis showed that the mutations identified in infantile patients caused rapid degradation of the GLB1 precursor. In contrast, at least one mutation identified in the GLB1 gene of juvenile or adult patients showed the presence of the GLB1 precursor. Western blot analysis also revealed that fibroblasts from some infantile patients had a markedly reduced amount of protective protein/cathepsin A (PPCA) (genotypes: p.R482H/p.R482H, p.R59C/frame-shift, p.R208C/p.T239M)...
- Subjects
LYSOSOMAL storage diseases; NEUROLOGICAL disorders; GANGLIOSIDOSES; PHENOTYPES; GENETIC mutation; FIBROBLASTS; PEDIATRICS; PATHOLOGY; GENETIC research
- Publication
Acta Paediatrica, 2008, p119
- ISSN
0803-5253
- Publication type
Article
- DOI
10.1111/j.1651-2227.2008.00657_4.x