[Recent advances in molecular genetics of GM2 gangliosidosis].

Recent advances in molecular genetics of GM2 gangliosidosis are reviewed. GM2 gangliosidosis is an autosomal recessive, neurodegenerative disease caused by a deficiency of beta-hexosaminidase (Hex, EC 3.2.1.52) A activity, resulting in accumulation of GM2 ganglioside in the lysosomes of neuronal cells. There are two catalytically active forms of this enzyme: Hex A, composed of one alpha and one beta subunits. Three forms of this disease, Tay-Sachs disease, Sandhoff disease, and GM2 activator deficiency, have been recognized according to whether the defect involves the alpha subunit, beta subunit, or GM2 activator protein, respectively. A number of gene abnormalities responsible for the disease have been identified and mutations specific for phenotypes and racial backgrounds are summarized. Recently, the murine models of human Tay-Sachs disease and Sandhoff disease have been produced. With the finding of dramatically clinical phenotypes in these mice, these models could be useful for research on the pathogenesis or therapy of these diseases.