The intron 7 donor splice site transition: a second Tay-Sachs disease mutation in French Canada.

Mutations at the hexosaminidase A (HEXA) gene which cause Tay-Sachs disease (TSD) have elevated frequency in the Ashkenazi Jewish and French-Canadian populations.
We report a novel TSD allele in the French-Canadian population associated with the infantile form of the disease.
The mutation, a G-- > A transition at the + 1 position of intron 7, abolishes the donor splice site.
Cultured human fibroblasts from a compound heterozygote for this transition (and for a deletion mutation) produce no detectable HEXA mRNA. The intron 7 + 1 mutation occurs in the base adjacent to the site of the adult-onset TSD mutation (G805A). In both mutations a restriction site for the endonuclease EcoRII is abolished.
Unambiguous diagnosis, therefore, requires allele-specific oligonucleotide hybridization to distinguish between these two mutant alleles.
The intron 7 + 1 mutation has been detected in three unrelated families.
Obligate heterozygotes for the intron 7 + 1 mutation were born in the Saguenay-Lac-St-Jean region of Quebec.
The most recent ancestors common to obligate carriers of this mutation were from the Charlevoix region of the province of Quebec.
This mutation thus has a different geographic centre of diffusion and is probably less common than the exon 1 deletion TSD mutation in French Canadians.
Neither mutation has been detected in France, the ancestral homeland of French Canada.. 
