Genealogy and geographical distribution of CFTR mutations in Saguenay Lac-Saint-Jean (Quebec, Canada)

Braekeleer, Marc De; Daigneault, J; Allard, Christian; Simard, Fernand; Aubin, G

doi:10.1080/03014469600004592

Cited by 9 publications

(6 citation statements)

References 6 publications

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“…In the SLSJ sample, where no MLIIIA cases were reported, the only mutation that can explain MLII phenotype is 3503_3504delTC because it is the only one that was observed in all the obligate carriers investigated. Similar observations were found in literature regarding SLSJ and cystic fibrosis (OMIM 219700), autosomal recessive spastic ataxia of Charlevoix-Saguenay (OMIM 270550) and tyrosinaemia type 1 (OMIM 276700) as examples (29)(30)(31). Specifically, in a group of 21 MLII patients of Israeli Arab-Muslim, Palestinian Arab-Muslim, Turkish and Irish origin, only 12 patients had the 3503_ 3504delTC mutation (11).…”

Section: Discussionsupporting

confidence: 87%

Mucolipidosis II: a single causal mutation in the N‐acetylglucosamine‐1‐phosphotransferase gene (GNPTAB) in a French Canadian founder population

et al. 2008

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Mucolipidosis (ML) II (I-cell disease) is a lysosomal storage disorder caused by a deficiency of UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase. MLII is an autosomal recessive disease with a carrier rate estimated at 1/39 in Saguenay-Lac-Saint-Jean (SLSJ) (Quebec, Canada), which is the highest frequency documented worldwide. To identify the causing mutation, we sequenced GNPTAB exons in 27 parents of 16 MLII-deceased children from the SLSJ region as obligatory and potential carriers. We also performed a genealogical reconstruction for each parent to evaluate consanguinity levels and genetic contribution of ancestors. Our goal was to identify which parameters could explain the high MLII frequency observed in the SLSJ population. A single mutation (c.3503_3504delTC) was found in all obligatory carriers. In addition, 11 apparent polymorphisms were identified. The mutation was not detected in genomic DNA of 50 unrelated controls. Genealogical data show six founders (three couples) with a higher probability of having introduced the mutation in the population. The frequency of the mutation was increased as a consequence of this founder effect and of the resulting population structure. We suggest that c.3503_3504delTC is the allele causing MLII in the SLSJ population, and its high carrier rate is most likely explained by a founder effect.

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Section: Discussionsupporting

confidence: 87%

Mucolipidosis II: a single causal mutation in the N‐acetylglucosamine‐1‐phosphotransferase gene (GNPTAB) in a French Canadian founder population

et al. 2008

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“…Analyses of kinship and inbreeding have been used previously to study both Mendelian and complex genetic traits. Thus, for example, it has been demonstrated, in the population we investigated here, that F and φ are higher in cystic fibrosis transmembrane conductance regulator mutation groups than in the general population (39). In the same population, it has also been shown that cases with a specific subset of late‐onset Alzheimer's disease are more inbred than controls and that they are more closely related among themselves than to the controls.…”

Section: Discussionmentioning

confidence: 70%

A Genealogical Study of Essential Hypertension with and without Obesity in French Canadians

et al. 2002

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HAMET. A genealogical study of essential hypertension with and without obesity in French Canadians. Obes Res. 2002;10:463-470. Objectives: To investigate genetic homogeneity in a set of hypertensive families and in subsets chosen for high and low prevalence of obesity; and to compare fasting insulin and lipids, ion transport, and water homeostasis in the obese and lean families. Research Methods and Procedures:The study was carried out in a relative population isolate of the Saguenay/Lac St. Jean region in Canada. Genetic homogeneity was evaluated with the mean coefficients of kinship () and inbreeding (F) computed with ascending genealogies. Serum insulin and lipids were measured after overnight fasting. Total body water was estimated with bioelectrical impedance. Sodiumlithium countertransport and sodium-potassium co-transport were determined in freshly isolated erythrocytes. Results: F and were increased in hypertensive families compared with families selected at random. F and were further increased within the subsets of obese and lean families. In addition, fasting insulin, total body water, sodiumlithium countertransport, and sodium-potassium co-transport were higher in the obese than in the lean families. The two subsets of families did not differ by fasting lipids. Discussion: In the Saguenay/Lac St. Jean population, the degree of genetic homogeneity was increased in families selected for hypertension, and it was further increased in subsets of hypertensive families with high and low prevalence of obesity. This suggests that hypertension in lean and obese individuals may represent, at least in part, separate genetic entities. Some of the extra genes shared in common within the subsets may contribute to their differences in body weight, insulin sensitivity, ion transport, and water homeostasis.

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“…We showed recently that the genealogies of 10 obligate carriers of the A455E mutation could be traced back to a common ancestor couple who got married in 1764 in Charlevoix, a neighboring county (De Braekeleer et al 1996). Furthermore, de Vries et al (1996 found that all 10 A455E mutations from Saguenay Lac-Saint-Jean that they studied were carried on the same haplotype of intragenic microsatellite markers (22-35-13).…”

Section: Introductionmentioning

confidence: 99%

Genotype-phenotype correlation in cystic fibrosis patients compound heterozygous for the A455E mutation

et al. 1997

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Cystic fibrosis (CF) has a high incidence in the French-Canadian population of Saguenay Lac-Saint-Jean (Quebec). The A455E mutation accounts for 8.3% of the CF chromosomes. This mutation was shown to be associated with a milder lung disease in the Dutch population. Twenty two CF patients distributed in 17 families and compound heterozygotes for the A455E mutation have been followed at the Clinique de Fibrose Kystique de Chicoutimi. Fourteen patients also carried the delta F508 mutation while the remaining eight patients had the 621 + 1G-->T mutation. Each patient was matched by sex and age to a patient homozygous for the delta F508 mutation. The pairs were analyzed for several clinical and laboratory variables. The A455E compound heterozygotes were diagnosed at a later age (P = 0.003) and had chloride concentrations at the sweat test lower than those homozygous for the delta F508 mutation (P = 0.007). More patients were pancreatic sufficient (P = 0.004). They had a higher Shwachman score (P = 0.001) and better pulmonary function tests (P < 0.02). CF patients compound heterozygous for the A455E mutation have a milder pancreatic and lung disease than the delta F508 homozygotes. Therefore, the A455E should be associated with a better prognosis.

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Genealogy and geographical distribution of CFTR mutations in Saguenay Lac-Saint-Jean (Quebec, Canada)

Cited by 9 publications

References 6 publications

Mucolipidosis II: a single causal mutation in the N‐acetylglucosamine‐1‐phosphotransferase gene (GNPTAB) in a French Canadian founder population

Mucolipidosis II: a single causal mutation in the N‐acetylglucosamine‐1‐phosphotransferase gene (GNPTAB) in a French Canadian founder population

A Genealogical Study of Essential Hypertension with and without Obesity in French Canadians

Genotype-phenotype correlation in cystic fibrosis patients compound heterozygous for the A455E mutation

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