GM1-gangliosidosis is a genetic neurological disorder caused by mutations in the 
lysosomal acid beta-galactosidase gene. While its phenotypic expression is 
complex, it is usually classified as being of infantile, juvenile, or adult 
form, on the basis of age at onset, the rate of symptomatic progression, and 
severity of central nervous system involvement. We have analyzed the acid 
beta-galactosidase gene in 12 Japanese patients from nine families. The aim was 
to identify mutations in individual patients and then to examine possible 
correlation between the mutations and the clinical phenotypes. Northern blotting 
studies with a full-length human beta-galactosidase cDNA showed that the mRNA 
ranged from undetectable to substantially decreased in the infantile patients 
but was normal in quantity and size in all juvenile and adult patients. Four 
distinct missense mutations have been identified, each limited to the respective 
clinical forms within our small-size samples. In the infantile patient with 
decreased but detectable mRNA, a point mutation was found resulting in 
Arg49----Cys. In the infantile patient with nearly undetectable mRNA, mutation 
Arg457----Ter was identified. The mutation Arg201----Cys was found in all four 
of the juvenile patients, while all six adult patients were homozygous for the 
point mutation Ile51----Thr. The mutations found in the juvenile and adult 
patients alter restriction sites in the normal gene and thus are amendable to 
quick screening. The prediction that these mutations are responsible for the 
clinical disease was confirmed by no expression of the catalytic activity of the 
mutant proteins in the COS-I cell expression system.(ABSTRACT TRUNCATED AT 250 
WORDS)