Chronic GM2 gangliosidosis type Sandhoff associated with a novel missense HEXB gene mutation causing a double pathogenic effect

We identified a novel c.1556A > G transition in exon 12 of the HEXB gene associated with chronic Sandhoff’s disease, changing a conserved aspartic acid to glycine at position 494 of the Hex β-subunit; moreover, RT-PCR showed aberrant exon 12 skipping, causing a frame-shift and premature stop codon, consequent to the disruption of an exonic splicing enhancer motif by the mutation. These data suggest that the c.1556 A > G transition would affect both HEXB mRNA processing and biochemical properties of the β-subunit.