Atypical beta galactosidase molecular composition in a juvenile GM1 gangliosidosis patient

GM1 gangliosidosis, that arises from beta-galactosidase (GLB1) deficiency, is a very rare lysosomal storage disease. The GLB1 gene encodes for two different proteins: GLB1 and elastin binding protein (EBP), a cell surface protein involved in elastic fiber assembly. We aim to characterize a GM1 gangliosidosis patient, affected by the juvenile form of the disease, presenting an atypical molecular analysis. The patient was characterized at a clinical and biochemical level and the GLB1 gene coding region and intron- exon boundaries were analyzed. Two mutations were identified: the new c.931G>A (p.Gly311Arg), and the known c.797A>G (p.Asn266Ser). Both mutations were characterized in silico and, surprisingly, the known mutation, unless exonic, could reasonably induce an aberrant splicing product. We deepened this hypothesis by Real time, RT PCR and immunofluorescence analyses. The hypothetic aberrant product induced by the c.797A>G (p.Asn266Ser) genetic lesion, missing four bases compared to the wild type transcript, was not identified. However, a reduction of EBP and GLB1 were identified at mRNA and/or protein level. We stress the importance to consider all the clinical and molecular aspects in analysing GM1 gangliosidosis patients in order to promisingly identify and characterize atypical molecular compositions.