Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio B patients: possible common origin for the prevalent p.R59H mutation among gypsies.

GM1-gangliosidosis and Morquio B disease are rare lysosomal storage disorders caused by beta-galactosidase deficiency due to mutations in the GLB1 gene. Three major clinical forms of GM1-gangliosidosis have been established on the basis of age of onset and severity of symptoms: infantile, late infantile/juvenile, and adult. We performed mutation analysis on 30 GM1-gangliosidosis and five Morquio B patients, mainly of Spanish origin, and all the causative mutations were identified. Thirty different mutations were found, 21 of which were novel. With the exception of two adults and one juvenile patient, all the GM1-gangliosidosis patients were affected by the infantile form. Clinical findings are presented for all patients. We report the association of the novel mutations p.T420K and p.L264S with the adult form and the juvenile form, respectively. In addition, the novel mutation p.Y83C was associated with Morquio B disease. Among the 30 GM1-gangliosidosis patients, 6 were of Gypsy origin (Roma). Moreover, those six Gypsy patients shared not only the same mutation (p.R59H) but also a common haplotype. This observation indicates a possible founder effect in this group and suggests that screening of the p.R59H mutation may be appropriate in GM1-gangliosidosis patients of Gypsy origin. This is the first exhaustive mutational analysis performed in a large group of Iberian GM1-gangliosidosis and Morquio B patients.