BACKGROUND GM2-gangliosidosis is a fatal neurodegenerative lysosomal storage disease (LSD) caused by deficiency of either β-hexosaminidase A (Hex-A) and β-hexosaminidase B (Hex-B) together, or the GM2 activator protein. Clinical signs can be variable and are not pathognomonic for the specific, causal deficiency. OBJECTIVES To characterize the phenotype and genotype of GM2-gangliosidosis disea...

The GM2 activator deficiency (also known as the AB variant), Tay-Sachs disease, and Sandhoff disease are the major forms of the GM2 gangliosidoses, disorders caused by defective degradation of GM2 ganglioside. Tay-Sachs and Sandhoff diseases are caused by mutations in the genes (HEXA and HEXB) encoding the subunits of beta-hexosaminidase A. The GM2 activator deficiency is caused by mutations in...

background: sandhoff disease is an autosomal recessive disorder caused by β-hexosaminidase deficiency and accumulation of gm2 ganglioside resulting in progressive motor neuron manifestations and death from respiratory failure and infections in infantiles. pathogenic mutations in hexb gene were observed which leads to enzyme activity reduction and interruption of normal metabolic cycle of gm2 ga...

GM2 gangliosidosis variant 0 (Sandhoff disease, SD) is a fatal, progressive neurodegenerative lysosomal storage disease caused by mutations of the HEXB gene. In canine SD, a pathogenic mutation (c.283delG) of the canine HEXB gene has been identified in toy poodles. In the present study, a TaqMan probe-based real-time PCR genotyping assay was developed and evaluated for rapid and large-scale gen...

The mutL gene of Salmonella typhimurium LT2 is required for dam-dependent methyl-directed DNA mismatch repair. We have cloned and sequenced the mutL gene of S. typhimurium LT2 and compared its sequence with those of the hexB gene product of the gram-positive bacterium Streptococcus pneumoniae and the PMS1 gene product of the yeast Saccharomyces cerevisiae. MutL was found to be quite similar to ...

Non-allelic homologous recombination (NAHR), non-homologous end joining (NHEJ), and microhomology-mediated replication-dependent recombination (MMRDR) have all been put forward as mechanisms to explain DNA rearrangements associated with genomic disorders. However, many nonrecurrent rearrangements in humans remain unexplained. To further investigate the mutation mechanisms of these copy number v...

Human lysosomal beta-hexosaminidases are dimeric enzymes composed of alpha and beta-chains, encoded by the genes HEXA and HEXB. They occur in three isoforms, the homodimeric hexosaminidases B (betabeta) and S (alphaalpha), and the heterodimeric hexosaminidase A (alphabeta), where dimerization is required for catalytic activity. Allelic variations in the HEXA and HEXB genes cause the fatal inbor...

Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative diseases resulting from the inability to catabolize GM2 ganglioside by beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit (Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B (beta beta homodimer) is also defective in Sandhoff disease. We previously developed mouse models of both disease...

Tay-Sachs or Sandhoff disease result from mutations in either the evolutionarily related HEXA or HEXB genes encoding respectively, the α- or β-subunits of β-hexosaminidase A (HexA). Of the three Hex isozymes, only HexA can interact with its cofactor, the GM2 activator protein (GM2AP), and hydrolyze GM2 ganglioside. A major impediment to establishing gene or enzyme replacement therapy based on H...