title: Molecular analysis of HEXA gene in Argentinean patients affected with Tay-Sachs disease: possible common origin of the prevalent c.459+5A>G mutation.
abstract: Tay-Sachs disease (TSD) is a recessively inherited disorder caused by the deficient activity of hexosaminidase A due to mutations in the HEXA gene. Up to date there is no information regarding the molecular genetics of TSD in Argentinean patients. In the present study we have studied 17 Argentinean families affected by TSD, including 20 patients with the acute infantile form and 3 with the sub-acute form. Overall, we identified 14 different mutations accounting for 100% of the studied alleles. Eight mutations were novel: 5 were single base changes leading to drastic residue changes or truncated proteins, 2 were small deletions and one was an intronic mutation that may cause a splicing defect. Although the spectrum of mutations was highly heterogeneous, a high frequency of the c.459+5G>A mutation, previously described in different populations was found among the studied cohort. Haplotype analysis suggested that in these families the c.459+5G>A mutation might have arisen by a single mutational event.
authors.affiliation: Regional Coordinator Centre for Rare Disease, University Hospital Santa Maria della Misericordia, Udine, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Zampieri
authors.forename: Annalisa
authors.initials: A
authors.lastname: Montalvo
authors.forename: Mariana
authors.initials: M
authors.lastname: Blanco
authors.forename: Irene
authors.initials: I
authors.lastname: Zanin
authors.forename: Hernan
authors.initials: H
authors.lastname: Amartino
authors.forename: Kristian
authors.initials: K
authors.lastname: Vlahovicek
authors.forename: Marina
authors.initials: M
authors.lastname: Szlago
authors.forename: Andrea
authors.initials: A
authors.lastname: Schenone
authors.forename: Gabriela
authors.initials: G
authors.lastname: Pittis
authors.forename: Bruno
authors.initials: B
authors.lastname: Bembi
authors.forename: Andrea
authors.initials: A
authors.lastname: Dardis
mesh_terms: D002648:Child; D015331:Cohort Studies; D005260:Female; D054818:Hexosaminidase A / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D013661:Tay-Sachs Disease / Q000235:genetics*
chemical_list: D054818:Hexosaminidase A