[Tay-Sachs disease].
GM2-gangliosidosis is a group of neurological disorders resulting from genetically defective catabolism, and consequent abnormal accumulation, of GM2-ganglioside. Three major types are distinguished: the B variant (Tay-Sachs disease), the O variant (Sandhoff disease), and the AB variant, caused by genetic abnormalities in the genes coding for the beta-hexosaminidase alpha- or beta-subunit, or the GM2-activator protein, respectively. A number of gene abnormalities responsible for Tay-Sachs disease have already been identified and the correlation between the beta-hexosaminidase alpha gene abnormality and the clinical phenotype has been explained in many cases. In the severest phenotype of Tay-Sachs disease (infantile form), mRNA of beta-hexosaminidase alpha subunit is not produced or is unstable such as in French Canadian patients or in Jewish patients with infantile Tay-Sachs disease, or the polypeptide does not have any catalytic activities because of the alteration of glycosylation such as the mutation of Glu482-to-Lys found in a Italian patient or the altered structure of polypeptide. The mutation identified in a large majority of the Japanese infantile Tay-Sachs disease patients, which is a G-to-T substitution at 3'-end of intron 5, generates a short mRNA with complete skipping of exon 6 and a polypeptide lacking 34 amino acids is generated but catalytically inactive. On the other hand, some active alpha beta dimers must be generated in patients with milder phenotypes of Tay-Sachs disease such as Gly269-to-Ser mutation in an adult form. Some of the mutations appear in high frequency among certain ethnic groups such as Ashkenazi Jewish patients and French Canadians.(ABSTRACT TRUNCATED AT 250 WORDS)
Tanaka
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Department of Pediatrics, Osaka City University, School of Medicine.
D017668:Age of Onset; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D009154:Mutation; D012333:RNA, Messenger; D013661:Tay-Sachs Disease / Q000145:classification / Q000209:etiology / Q000235:genetics*; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
D012333:RNA, Messenger; D001619:beta-N-Acetylhexosaminidases