title: The intron 7 donor splice site transition: a second Tay-Sachs disease mutation in French Canada.
abstract: 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.
authors: Montreal Children's Hospital Research Institute, McGill University, Montreal, Quebec, Canada.
authors: P
authors: P
authors: Hechtman
authors: B
authors: B
authors: Boulay
authors: M
authors: M
authors: De Braekeleer
authors: E
authors: E
authors: Andermann
authors: S
authors: S
authors: Melançon
authors: J
authors: J
authors: Larochelle
authors: C
authors: C
authors: Prevost
authors: F
authors: F
authors: Kaplan
mesh_terms: D001483:Base Sequence; D004277:DNA, Single-Stranded; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D006579:Heterozygote; D054818:Hexosaminidase A; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011792:Quebec; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D013661:Tay-Sachs Disease / Q000235:genetics*; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics
chemical_list: D004277:DNA, Single-Stranded; D012333:RNA, Messenger; D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases