Molecular pathology of infantile GM1 gangliosidosis

Abstract

The lysosomal storage disorder GM1 gangliosidosis is a genetic neurological disorder caused by a complete or partial deficiency of acid β-galactosidase; it is usually classified as being of infantile, juvenile or adult forms. Infantile GM1 gangliosidosis is relatively common in the Maltese population, with a heterogeneous incidence of 3.3 % and 0.027 % heterozygotes. The molecular lesion associated with this pathology, was studied in two unrelated Maltese families. Fragments containing all the exons and flanking regions of the β-galactosidase gene, were amplified using Polymerase Chain Reaction and then sequenced. A variant was identified and denoted Spl 7. This double point mutation, CA->GT, lies within the IVS 7 of β-galactosidase gene, at position 9 and 10 bp downstream of the 3' end of exon 7, the 3' end is at cDNA position 842. Taq I restriction enzyme digestion, confirmed this mutation. In addition Bfal restriction enzyme digestion, also confirmed the presence of the two mutations in Cis. This variant was confirmed to be non-polymorphic by Taq I digestion of a 100 random chromosomes. Other variants are present in the Maltese population, but they were not characterised in this study. Urinary oligosaccharides analysis was used to test Maltese families for the presence high amount of oligosaccharides, comparing the level of the resulted patterns with the location of maltotetraose (G4). The result was consistent with the molecular study.