Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common mutation among Japanese adult/chronic cases.

Molecular analysis of the human beta-galactosidase gene revealed six different mutations in 10 of 11 Japanese GM1-gangliosidosis patients.They were the only abnormalities in each allele examined in this study.A 165-nucleotide duplication (positions 1103-1267) was found in two infantile patients, producing an abnormally large mRNA;one patient was probably a homozygote, and the other was a heterozygote of this mutation.The other two infantile patients had different mutations;a 123 Gly(GGG)----Arg(AGG) mutation in one patient and a 316 Tyr(TAT)----Cys(TGT) mutation in the other.A 201 Arg(CGC)----Cys(TGC) mutation, eliminating a BspMI site, was detected in a late-infantile/juvenile patient;the restriction-site analysis of amplified genomic DNA confirmed his heterozygosity for this mutation.A 51 Ile(ATC)----Thr(ACC) mutation was found in all five adult/chronic patients examined in this study.It created a SauI site, and restriction-site analysis confirmed that four patients were homozygous mutants.The other was a compound heterozygote for this mutation and another 457 Arg(CGA)----Gln(CAA) mutation.These mutant genes expressed markedly decreased or completely deficient enzyme activities in beta-galactosidase-deficient human fibroblasts transformed by adenovirus-SV40 recombinants.We conclude that gene mutations are heterogeneous in GM1-gangliosidosis but that the 51 Ile(ATC)----Thr(ACC) mutation is common among the Japanese adult/chronic cases.Genotype-phenotype correlations in GM1-gangliosidosis are briefly discussed.