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.
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.
Landels
E C
EC
Paediatric Research Unit, UMDS, Guy's Hospital, London.
Green
P M
PM
Ellis
I H
IH
Fensom
A H
AH
Kaback
M M
MM
Lim-Steele
J
J
Zeiger
K
K
Levy
N
N
Bobrow
M
M
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*
D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases