The intron 7 donor splice site transition: a second Tay-Sachs disease mutation in French Canada |
| |
Authors: | Peter Hechtman Bernard Boulay Marc De Braekeleer Eve Andermann Serge Melançon Jean Larochelle Claude Prevost Feige Kaplan |
| |
Institution: | (1) Montreal Children's Hospital Research Institute, McGill University, 2300 Tupper Street, H3H 1P3 Montreal, Quebec, Canada;(2) Biology Department Centre for Human Genetics, McGill University, Montreal, Canada;(3) Department de Science Humaine, Université de Quebec, Chicoutimi, Quebec, Canada;(4) Department of Neurogenetics, Montreal Neurological Hospital, Montreal, Quebec, Canada;(5) Department de Genetique Humaine, Hôpital St-Justine, Montreal, Quebec, Canada;(6) Hôpital de Chicoutimi, Chicoutimi, Quebec, Canada;(7) Montreal Children's Hospital Research Institute, McGill University, 2300 Tupper Street, H3H 1P3 Montreal, Quebec, 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 GA 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. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|