title: Identification of 14 novel GLB1 mutations, including five deletions, in 19 patients with GM1 gangliosidosis from South America.
abstract: GM1 gangliosidosis is a lysosomal storage disorder caused by the absence or reduction of lysosomal beta-galactosidase activity because of mutations in the GLB1 gene. Three major clinical forms have been established: type I (infantile), type II (late infantile/juvenile) and type III (adult). A mutational analysis was performed in 19 patients with GM1 gangliosidosis from South America, mainly from Argentina. Two of them were of Gypsy origin. Main clinical findings of the patients are presented. All 38 mutant alleles were identified: of the 22 different mutations found, 14 mutations are described here for the first time. Among the novel mutations, five deletions were found. Four of them are relatively small (c.435_440delTCT, c.845_846delC, c.1131_1145del15 and c.1706_1707delC), while the other one is a deletion of 1529 nucleotides that includes exon 5 and is caused by an unequal crossover between intronic Alu sequences. All the described patients with GM1 gangliosidosis were affected by the infantile form, except for four unrelated patients classified as type II, III, and II/III (two cases). The two type II/III patients bore the previously described p.R201H mutation, while the adult patient bore the new p.L155R. The juvenile patient bore two novel mutations: p.S434L and p.G554E. The two Gypsy patients are homozygous for the p.R59H mutation as are all Gypsy patients previously genotyped.
authors.affiliation: Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Santamaria
authors.forename: M
authors.initials: M
authors.lastname: Blanco
authors.forename: A
authors.initials: A
authors.lastname: Chabás
authors.forename: D
authors.initials: D
authors.lastname: Grinberg
authors.forename: L
authors.initials: L
authors.lastname: Vilageliu
mesh_terms: D000328:Adult; D000483:Alleles; D001118:Argentina; D001483:Base Sequence; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons; D016537:Gangliosidosis, GM1 / Q000175:diagnosis / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D009154:Mutation; D017384:Sequence Deletion; D001616:beta-Galactosidase / Q000235:genetics*
chemical_list: C061901:GLB1 protein, human; D001616:beta-Galactosidase