title: Molecular analysis of the HEXA gene in Italian patients with infantile and late onset Tay-Sachs disease: detection of fourteen novel alleles.
abstract: Tay-Sachs disease (TSD) is a recessively inherited disorder caused by the hexosaminidase A deficiency. We report the molecular characterization performed on 31 Italian patients, 22 with the infantile, acute form of TSD and nine patients with the subacute juvenile form, biochemically classified as B1 Variant. Of the 29 different alleles identified, fourteen were due to 15 novel mutations, two being in-cis on a new complex allele. The new alleles caused four frameshifts, three premature stop codons, three amino acid changes, two amino acid deletions and two splicing alterations. As previously reported, the c.533G>A (p.R178H) mutation was present either in homozygosity or as compound heterozygote, in all the patients with the late onset TSD form (B1 Variant); the allele frequency in this group is discussed by comparison with that found in infantile TSD.
authors.affiliation: Unità di Malattie Metaboliche, IRCCS Burlo Garofolo, Trieste, Italy.
authors.forename: Anna Lisa E
authors.initials: AL
authors.lastname: Montalvo
authors.forename: Mirella
authors.initials: M
authors.lastname: Filocamo
authors.forename: Kristian
authors.initials: K
authors.lastname: Vlahovicek
authors.forename: Andrea
authors.initials: A
authors.lastname: Dardis
authors.forename: Susanna
authors.initials: S
authors.lastname: Lualdi
authors.forename: Fabio
authors.initials: F
authors.lastname: Corsolini
authors.forename: Bruno
authors.initials: B
authors.lastname: Bembi
authors.forename: Maria Gabriela
authors.initials: MG
authors.lastname: Pittis
mesh_terms: D000483:Alleles; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D054818:Hexosaminidase A; D006801:Humans; D007223:Infant; D007558:Italy; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D013661:Tay-Sachs Disease / Q000235:genetics*; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
chemical_list: D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases