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

Anna Caciotti , Scott C. Garman (1) , Yadilette Rivera-Colón (1) , Elena Procopio , Serena Catarzi , Lorenzo Ferri , Carmen Guido , Paola Martelli , Rossella Parini (2) , Daniela Antuzzi , Roberta Battini (3) , Michela Sibilio (4) , Alessandro Simonati (5) , Elena Fontana (5) , Alessandro Salviati (5) , Gulcin Akinci (6) , Cristina Cereda (7) , Carlo Dionisi-Vici (8) , Francesca Deodato (8) , Adele d'Amico (8) , Alessandra d'Azzo (9) , Enrico Bertini (10) , Mirella Filocamo , Maurizio Scarpa (11) , Maja Di Rocco (12) , Cynthia J. Tifft (13) , Federica Ciani , Serena Gasperini , Elisabetta Pasquini , Renzo Guerrini , Maria Alice Donati , Amelia Morrone (14)

1 Department of Biochemistry & Molecular Biology
2 San Gerardo Hospital
3 Department of Developmental Neuroscience
4 Department of Pediatrics
5 Department of Neurological and Visual Sciences
6 Department of Pediatrics
7 IRCCS Neurological Institute "C. Mondino"
8 Division of Metabolism
9 Dep. of Genetics
10 Department of Laboratory Medicine
11 Department of Pediatrics
12 Dept of Pediatrics
13 Division of Genetics & Metabolism
14 Department of Sciences for Woman and Child's Health

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 () 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.

Mots clés: (GLB1); (NB-DNJ; (EBP); (PPCA); (NEU1); beta-galactosidase; GM1- gangliosidosis; Morquio B; mutation update; homology modelling

Domaines: Biochimie, Biologie Moléculaire

Anna Caciotti, Scott C. Garman, Yadilette Rivera-Colón, Elena Procopio, Serena Catarzi, et al.. GM1 gangliosidosis and Morquio B disease: An update on genetic alterations and clinical findings. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2011, ⟨10.1016/j.bbadis.2011.03.018⟩. ⟨hal-00694873⟩