title: Collaborative study of the molecular epidemiology of Tay-Sachs disease in Europe.
abstract: Tay-Sachs disease is a lipidosis due to the deficiency of the lysosomal hexosaminidase A. In order to understand the molecular mechanisms of this enzyme deficiency we studied 42 patients of different ethnic origins diagnosed in Europe. The strategy used consists in HEXA cDNA amplification followed by allele-specific oligonucleotide analysis for the frequent mutations, and by chemical cleavage mismatch and denaturing gradient gel electrophoresis for the detection of new mutations. 90% of alleles were clarified in this way, showing a high heterogeneity of HEXA lesions in Tay-Sachs disease. 28 different mutations were found, 20 being identified for the first time in this group of patients.
authors.affiliation: Institut Cochin de Génétique Moléculaire, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Akli
authors.forename: J
authors.initials: J
authors.lastname: Boue
authors.forename: K
authors.initials: K
authors.lastname: Sandhoff
authors.forename: W
authors.initials: W
authors.lastname: Kleijer
authors.forename: E
authors.initials: E
authors.lastname: Vamos
authors.forename: E
authors.initials: E
authors.lastname: Young
authors.forename: R
authors.initials: R
authors.lastname: Gatti
authors.forename: P
authors.initials: P
authors.lastname: Di Natale
authors.forename: J
authors.initials: J
authors.lastname: Motte
authors.forename: M T
authors.initials: MT
authors.lastname: Vanier
mesh_terms: D000328:Adult; D000483:Alleles; D001482:Base Composition; D001483:Base Sequence; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D015226:Dinucleoside Phosphates / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D016368:Frameshift Mutation; D005838:Genotype; D054818:Hexosaminidase A; D006801:Humans; D007223:Infant; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics; D015345:Oligonucleotide Probes; D010641:Phenotype; D017354:Point Mutation; D012326:RNA Splicing; D017384:Sequence Deletion; D013661:Tay-Sachs Disease / Q000453:epidemiology* / Q000235:genetics*; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
chemical_list: D015226:Dinucleoside Phosphates; D054818:Hexosaminidase A; D009692:Nucleic Acid Heteroduplexes; D015345:Oligonucleotide Probes; D001619:beta-N-Acetylhexosaminidases; C015772:CpG dinucleotide