title: Further investigation of the HEXA gene intron 9 donor splice site mutation frequently found in non-Jewish Tay-Sachs disease patients from the British Isles.
abstract: In a previous study we found that a Tay-Sachs disease (TSD) causing mutation in the intron 9 donor splice site of the HEXA gene occurs at high frequency in non-Jewish patients and carriers from the British Isles. It was found more frequently in subjects of Irish, Scottish, and Welsh origin compared with English origin (63% and 31% respectively). We have now tested, in a blind study, 26 American TSD carriers and 28 non-carriers who have British ancestry for the intron 9 splice site mutation. Six of the carriers and none of the controls were positive for the mutation. All six had Irish ancestry, compared with nine of the 20 other (intron 9 mutation negative) TSD carriers (p < 0.05). These results confirm the previously found high frequency of the intron 9 mutation in non-Jewish TSD families of British Isles, particularly Irish, origin, and reinforce the need to screen such families for this mutation.
authors.affiliation: Paediatric Research Unit, UMDS, Guy's Hospital, London.
authors.forename: E C
authors.initials: EC
authors.lastname: Landels
authors.forename: P M
authors.initials: PM
authors.lastname: Green
authors.forename: I H
authors.initials: IH
authors.lastname: Ellis
authors.forename: A H
authors.initials: AH
authors.lastname: Fensom
authors.forename: M M
authors.initials: MM
authors.lastname: Kaback
authors.forename: J
authors.initials: J
authors.lastname: Lim-Steele
authors.forename: K
authors.initials: K
authors.lastname: Zeiger
authors.forename: N
authors.initials: N
authors.lastname: Levy
authors.forename: M
authors.initials: M
authors.lastname: Bobrow
mesh_terms: D004739:England / Q000208:ethnology; D054818:Hexosaminidase A; D006801:Humans; D007438:Introns; D007494:Ireland / Q000208:ethnology; D017354:Point Mutation; D012326:RNA Splicing; D012606:Scotland / Q000208:ethnology; D013661:Tay-Sachs Disease / Q000208:ethnology* / Q000235:genetics*; D014481:United States; D014852:Wales / Q000208:ethnology; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
chemical_list: D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases