The incidence and carrier frequency of Tay-Sachs disease in the French-Canadian population of Quebec based on retrospective data from 24 years, 1992-2015.

Tay-Sachs disease (TSD) is a hereditary neurodegenerative condition inherited through an autosomal recessive pattern. The incidence and carrier frequency of infantile TSD were found to be increased among French Canadians in specific areas of the province of Quebec or calculated from New England populations with French-Canadian heritage. No accurate infantile TSD carrier frequency for the whole French-Canadian population in Quebec has been published. In this study, we estimate the incidence and carrier frequency of infantile TSD in the Quebec French-Canadian population. The number of TSD cases was ascertained during the 1992-2015 period, as well as the number of births to mothers whose language of use is French. Seven cases of TSD have been diagnosed in Quebec during the period of ascertainment. This corresponds to an incidence of 1/218,144, which in turn corresponds to a carrier frequency of 1/234. In the same 24-year period, there are two French-Canadian couples who had a fetus prenatally diagnosed with TSD. If these cases are included, the incidence of TSD in the French-Canadian population of Quebec is 1/169,668 and the carrier frequency 1/206. These findings can be used for genetic counseling and policy decisions regarding carrier screening for TSD in populations of French-Canadian descent.

A 10376 bp deletion of FECH gene responsible for erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP, MIM 177000) is an autosomal dominant disease with incomplete penetrance since the phenotypic expression requires coinheritance of a null allele and a wild-type low expressed allele of Ferrochelatase gene (FECH). In this study, we identify a peculiar mutation in a young Canadian patient of Italian origin. The patient had clinical and biochemical symptoms of EPP, the wild-type low expressed allele but at preliminary analysis no mutation in the promoter, in the entire coding region and in the splice junctions of the gene. Family studies of seven most common polymorphisms along the gene established absence of Mendelian segregation for the promoter polymorphism only. The intron 1 polymorphism appeared in heterozygosis suggesting an hypothetical deletion in the first region of the gene. In order to identify the size of this deletion, single nucleotide polymorphisms (SNPs) analysis was extended to the upstream N-asparaginyl-tRNA synthetase gene (NARS). We analyzed two polymorphisms in the last exon of this gene and a dizigous region was found in the patient. A Long-PCR with primers located in previously fixed heterozygous regions showed a 10,376 bp deletion (c.1-7887_67+2422del) that included a portion of the upstream intergenic region, the promoter, the exon 1 and a portion of intron 1. RNA analysis demonstrated that the lack of the entire promoter prevents the expression of the mutated allele, in fact the expression of the Ferrochelatase gene was decreased by half in the subjects carrying only the mutation compared to control.