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The Saguenay-Lac-Saint-Jean (SLSJ) region located in the province of Quebec was settled in the 19th century by pioneers issued from successive migration waves starting in France in the 17th century and continuing within Quebec until the beginning of the 20th century. The genetic structure of the SLSJ population is considered to be the product of a triple founder effect and is characterised by a higher prevalence of some rare genetic diseases. Several studies were performed to elucidate the historical, demographic and genetic background of current SLSJ inhabitants to assess the origins of these rare disorders and their distribution in the population. Thanks to the development of new sequencing technologies, the genes and the variants responsible for the most prevalent conditions were identified. Combined with other resources such as the BALSAC population database, identifying the causal genes and the pathogenic variants allowed to assess the impacts of some of these founder mutations on the population health and to design precision medicine public health strategies based on carrier testing. Furthermore, it stimulated the establishment of many public programmes.We report here a review and an update of a subset of inherited disorders and founder mutations in the SLSJ region. Data were collected from published scientific sources. This work expands the knowledge about the current frequencies of these rare disorders, the frequencies of other rare genetic diseases in this population, the relevance of the carrier tests offered to the population, as well as the current available treatments and research about future therapeutic avenues for these inherited disorders., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The closing plenary of the colloquium was an occasion for exchange between the four panelists and the participants. The panelists included Luc Berghmans, a doctor and director of the regional health observatory of Hainaut, Belgium; Louise Bouchard, a sociologist and professor in the Sociology and Anthropology Department, University of Ottawa, Canada; Michel O’Neill, a sociologist and professor at the Faculty of Nursing Sciences, Laval University, Quebec City, Canada; and Philippe Lorenzo, director general of IREPS, the regional bureau for health education and promotion of Picardie in Amiens, France. Louise Potvin, who moderated the plenary, provides the summary that follows. During the colloquium, three main questions were debated: 1. At what point should health be placed at the forefront of local actions, if we wish to promote the values of equity? 2. How should actions at the local, regional, national and global levels be organized and articulated? Who are the partners, and what forms of governance need to be put into place? 3. What are the parameters needed in order to define the roles, tasks and competencies of the implementers of local and regional health programs, the architects of change? Each panelist had to respond to two out of the three questions. We report on the answers that panelists gave to these questions. As it is impossible to verify the exactitude of information given by audience members in support of their viewpoints, only the content of the remarks is given, without mentioning the examples that were provided.

Background: Zellweger syndrome (ZS) is a peroxisome biogenesis disorder due to mutations in any one of 13 PEX genes. Increased incidence of ZS has been suspected in French-Canadians of the Saguenay-Lac-St-Jean region (SLSJ) of Quebec, but this remains unsolved., Methods: We identified 5 ZS patients from SLSJ diagnosed by peroxisome dysfunction between 1990-2010 and sequenced all coding exons of known PEX genes in one patient using Next Generation Sequencing (NGS) for diagnostic confirmation., Results: A homozygous mutation (c.802_815del, p.[Val207_Gln294del, Val76_Gln294del]) in PEX6 was identified and then shown in 4 other patients. Parental heterozygosity was confirmed in all. Incidence of ZS was estimated to 1 in 12,191 live births, with a carrier frequency of 1 in 55. In addition, we present data suggesting that this mutation abolishes a SF2/ASF splice enhancer binding site, resulting in the use of two alternative cryptic donor splice sites and predicted to encode an internally deleted in-frame protein., Conclusion: We report increased incidence of ZS in French-Canadians of SLSJ caused by a PEX6 founder mutation. To our knowledge, this is the highest reported incidence of ZS worldwide. These findings have implications for carrier screening and support the utility of NGS for molecular confirmation of peroxisomal disorders.

Background: The authors investigated the acceptability to women of the preventive strategies available for dealing with hereditary breast/ovarian carcinoma in France, the United Kingdom, and Canada, countries selected because of their cultural differences. The authors aimed to discover the existence of specific factors that may affect acceptability of these preventative measures., Methods: A cross-sectional, multicenter survey was conducted in Marseilles, France (n = 141), in Manchester, England (n = 130), and in Montreal, Quebec (n = 84). All of the women attending cancer genetic clinics for the first time because of a family history of breast-ovarian carcinoma completed a self-administered questionnaire before their clinic consultation., Results: Variations in responses to different preventative options presented on the questionnaire were seen within the sample of patients considered as a whole. The highest levels of acceptability were obtained for mammographic screening (87%) and chemoprevention (58%). In contrast, prophylactic oophorectomy and prophylactic mastectomy were thought to be acceptable at an early age (before 35 years), an age associated with the highest prophylactic efficacy, by only 19% and 16% of the respondents, respectively. After multivariate adjustment, the statistical data showed that the British respondents were more in favor of oophorectomy (P < 0.0001) and more in favor of chemoprevention than the French (P < 0.001) and the Canadian respondents (P < 0.001). The British (overall adjusted response [OR(adj)] = 3.9; P < 0.001) and Canadian respondents (OR(adj) = 3; P < 0.01) were more in favor of prophylactic mastectomy than the French. The cumulated acceptability of mammography before the age of 40 years was found to be greater in the French (OR(adj) = 2.8; P < 0.01) and Canadian (OR(adj) = 3.1; P < 0.05) samples than in the British sample., Conclusion: These results demonstrated the existence of international variations in the acceptability of the preventive strategies available for women at risk for hereditary breast/ovarian carcinoma. Therefore, these results suggested that when establishing medical recommendations or planning public health interventions, physicians must integrate the population's perception of advantages and drawbacks with the patient's individual decision making., (Copyright 2001 American Cancer Society.)

The authors discuss the results of a survey of the attitudes of Canadian and French (Picardie, Nord-Pas de Calais) physicians toward selective abortion of fetal anomalies detected by ultrasound, amniocentesis, or chorionic villus sampling. The study documents the threshold of acceptability of abortion of fetuses with selected anomalies, as well as the physicians' own perceptions of their role in the decision to abort. While there was no consensus among all Canadian physicians regarding the acceptability of abortion, more than 55 percent from France and Quebec would accept selective abortion of a fetus affected with trisomy 21, Duchenne muscular dystrophy, cystic fibrosis, Huntington's chorea, or spina bifida. In the province of Quebec, Anglophone physicians showed a greater acceptance of abortion than did their French-speaking colleagues. In reference to the physician's role in the decision to abort, French physicians are more directive than North American physicians. Cultural predispositions may explain these differences in attitudes.

This article discusses the results of a study of the stand and attitudes of physicians from the Picardie, Nord-Pas-de-Calais region in France and the province of Quebec (Canada) regarding abortion following the diagnosis of a fetal anomaly by ultrasound, amniocentesis, or chorionic villus sampling. The study examined the degree of acceptability of abortion for several specific conditions as well as the physicians' perceptions of their role in the women's decision to abort. The study shows a consensus (over 75 per cent of the physicians surveyed) for aborting a fetus with trisomy 21. There is a similar consensus, except among Francophones in Quebec, for muscular dystrophy, cystic fibrosis, and Huntington disease. Conversely, there is no consensus (below 60 per cent) for several anomalies. In these cases, Quebec Anglophone physicians find abortion more acceptable than Quebec Francophone or French physicians. Concerning the role of the practitioners in the decision to abort, physicians in France tend to be much more directive than their overseas colleagues. Several hypotheses are suggested to explain the difference between the three groups surveyed.