More than one mutant allele causes infantile Tay-Sachs disease in French-Canadians.
Two Tay-Sachs disease (TSD) patients of French-Canadian origin were shown by Myerowitz and Hogikyan to be homozygous for a 7.6-kb deletion mutation at the 5' end of the hexosaminidase A alpha-subunit gene. In order to determine whether all French-Canadian TSD patients were homozygotes for the deletion allele and to assess the geographic origins of TSD in this population, we ascertained 12 TSD families of French-Canadian origin and screened for occurrence of mutations associated with infantile TSD. DNA samples were obtained from 12 French-Canadian TSD families. Samples were analyzed using polymerase-chain-reaction (PCR) amplification followed by hybridization to allele-specific oligonucleotides (ASO) or by restriction analysis of PCR products. In some cases Southern analysis of genomic DNA was performed. Eighteen of the 22 independently segregating mutant chromosomes in this sample carried the 7.6-kb deletion mutation at the 5' end of the gene. One chromosome carried the 4-nucleotide insertion in exon 11 (a "Jewish" mutation). In this population no individuals were detected who had the substitution at the splice junction of exon 12 previously identified in Ashkenazi Jews. One chromosome carried an undescribed B1 mutation; this allele came from a parent of non-French-Canadian origin. Patients in three families carried TSD alleles different from any of the above mutations. The 5' deletion mutation clusters in persons originating in southeastern Quebec (Gaspé) and adjacent counties of northern New Brunswick.
Hechtman
P
P
Research Institute, McGill University-Montreal Children's Hospital, Quebec, Canada.
Kaplan
F
F
Bayleran
J
J
Boulay
B
B
Andermann
E
E
de Braekeleer
M
M
Melançon
S
S
Lambert
M
M
Potier
M
M
Gagné
R
R
D000483:Alleles; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D015994:Incidence; D007585:Jews / Q000235:genetics; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011792:Quebec / Q000453:epidemiology; D013661:Tay-Sachs Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*