title: Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common mutation among Japanese adult/chronic cases.
abstract: 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.
authors.affiliation: Department of Clinical Genetics, Tokyo Metropolitan Institute of Medical Science, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: A
authors.initials: A
authors.lastname: Oshima
authors.forename: M
authors.initials: M
authors.lastname: Shimmoto
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuhara
authors.forename: H
authors.initials: H
authors.lastname: Sakuraba
authors.forename: N
authors.initials: N
authors.lastname: Yanagisawa
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002478:Cells, Cultured; D002648:Child; D002908:Chronic Disease; D003001:Cloning, Molecular; D005677:G(M1) Ganglioside; D005733:Gangliosidoses / Q000201:enzymology / Q000235:genetics*; D005796:Genes; D006801:Humans; D007223:Infant; D007564:Japan; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D001616:beta-Galactosidase / Q000235:genetics*
chemical_list: D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D005677:G(M1) Ganglioside; D001616:beta-Galactosidase