Report on the p.Ser489X (p.Ser489*) CFTR mutation, a variant with severe associated phenotype and high prevalence in a Quebec French-Canadian cystic fibrosis patient population

Bie, Isabelle De; Agatep, Ron; Scott, Patrick; Ruchon, Andrea

doi:10.1038/gim.2012.57

Cited by 6 publications

(5 citation statements)

References 12 publications

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“…Our study findings indicate an underutilization of genetic-counseling services. Although few studies have examined consumer decisions to seek genetic counseling, this result is consistent with a survey based study conducted by Kaufman et al , [22] in which a mere 1% of participants sought out genetic counseling when interpreting their results [23]. Our study result may be explained in part by the biased perception of the students undergoing personal genotyping that, unlike the general population, they possessed sufficient knowledge to interpret their results.…”

Section: Discussionsupporting

confidence: 89%

“…Consistent with the few empirical studies that have examined the behavioral responses of consumers of DTC genetic testing services, our study results provide little evidence to suggest that the mere provision of genetic information alone results in widespread changes in health behaviors [2,23]. Although students did report their intention to make modest behavioral changes as a result of risk predictions of complex diseases and conditions shortly after receiving their results, none had made any clinical changes or pursued follow-up care with healthcare providers 6 months later.…”

Section: Discussionsupporting

confidence: 68%

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Personal genome testing in medical education: student experiences with genotyping in the classroom

et al. 2013

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BackgroundDirect-to-consumer (DTC) personal genotyping services are beginning to be adopted by educational institutions as pedagogical tools for learning about human genetics. However, there is little known about student reactions to such testing. This study investigated student experiences and attitudes towards DTC personal genome testing.MethodsIndividual interviews were conducted with students who chose to undergo personal genotyping in the context of an elective genetics course. Ten medical and graduate students were interviewed before genotyping occurred, and at 2 weeks and 6 months after receiving their genotype results. Qualitative analysis of interview transcripts assessed the expectations and experiences of students who underwent personal genotyping, how they interpreted and applied their results; how the testing affected the quality of their learning during the course, and what were their perceived needs for support.ResultsStudents stated that personal genotyping enhanced their engagement with the course content. Although students expressed skepticism over the clinical utility of some test results, they expressed significant enthusiasm immediately after receiving their personal genetic analysis, and were particularly interested in results such as drug response and carrier testing. However, few reported making behavioral changes or following up on specific results through a healthcare provider. Students did not report utilizing genetic counseling, despite feeling strongly that the 'general public' would need these services. In follow-up interviews, students exhibited poor recall on details of the consent and biobanking agreements, but expressed little regret over their decision to undergo genotyping. Students reported mining their raw genetic data, and conveyed a need for further consultation support in their exploration of genetic variants.ConclusionsPersonal genotyping may improve students' self-reported motivation and engagement with course material. However, consultative support that is different from traditional genetic counseling will be necessary to support students. Before incorporating personal genotyping into coursework, institutions should lead multi-disciplinary discussion to anticipate issues and incorporate teaching mechanisms that engage the ethical, legal, and social implications of personal genotyping, including addressing those found in this study, to go beyond what is offered by commercial providers.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 68%

Personal genome testing in medical education: student experiences with genotyping in the classroom

et al. 2013

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“…Between 1608 and 1759, the colonization of Canada by the French brought about 8,500 pioneers to the Saint‐Lawrence Valley, once known as ‘Nouvelle‐France’, and was stopped by the British conquest of 1759 (De Bie, Agatep, Scott, & Ruchon, 2012; De Braekeleer & Dao, 1994; Laberge et al, 2005). In the 18th century, descendants of French pioneers from Acadia (corresponding to the current Canadian provinces of New Brunswick, Nova‐Scotia and Prince‐Edward Island) and American Loyalists settled in Quebec (De Bie et al, 2012; Laberge et al, 2005). In the 19th century, immigration occurred mostly from Scotland, Ireland, and England; and more recently in the 20th and 21st century, immigration came from diverse countries.…”

Section: Discussionmentioning

confidence: 99%

“…American Loyalists settled in Quebec (De Bie et al, 2012;Laberge et al, 2005). In the 19th century, immigration occurred mostly from Scotland, Ireland, and England; and more recently in the 20th and 21st century, immigration came from diverse countries.…”

Section: Limitations Of This Studymentioning

confidence: 99%

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

Sillon

Allard

Drury

et al. 2020

Journal of Genetic Counseling

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Tay-Sachs disease (TSD) is an autosomal recessive neurodegenerative disorder. It results from pathogenic variants in the HEXA gene that lead to deficient activity of the lysosomal β-hexosaminidase A enzyme (HEXA). HEXA consists of an α and a β subunit, encoded by the HEXA and the HEXB gene, respectively. When a patient is homozygous for a HEXA pathogenic variant, GM2 gangliosides are not hydrolyzed, accumulate in neuronal lysosomes and trigger progressive neuronal dysfunction, which begins around 2-6 months of age for infantile TSD and leads to complete disability and death, usually by 3-5 years of age (Gravel et al., 2001; Kaback & Desnick, 2001; Sutton, 2002). A diagnosis of infantile TSD is usually made before a child's third birthday on the basis of absent or significantly reduced level of HEXA activity measured through biochemical testing (Kaback & Desnick, 2001). Molecular analysis can confirm

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“…Several short-term real-world studies with a follow-up period ranging from 16 weeks up to 1 year after CFTR modulator initiation already suggested that the effectiveness of dual CFTR-modulators may be less strong than in trials and confirmed individual variability of treatment responses in a real-world setting [11,13,[68][69][70][71][72][73][74]. Yet the body of long-term real-world evidence after the first year of treatment is still limited, which is needed to estimate the impact of CFTR modulating therapies on individual CF disease progression.…”

Section: Long-term Efficacy and Real-world Outcomesmentioning

confidence: 99%

Cystic Fibrosis: a real-world challenge to predict individual outcomes

Muilwijk

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Cystic Fibrosis (CF) is a rare monogenic multisystem disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. More than 2000 different CFTR variants have been identified that differentially affect CFTR protein function. As a result, CF disease manifestations and response to recently developed CFTR-modulating treatments is highly variable among individuals. Without an effective treatment, people with CF can die at a young age. To develop and select the best personalized therapy for all people with CF, we need more sensitive tests and outcome measures to predict long-term disease progression and response to CFTR-modulating drugs in real-life practice. This thesis showed that the forskolin-induced swelling (FIS) assay of intestinal organoids is associated with long-term CF disease progression in multiple organs, including long-term lung function decline and the odds of developing CF-related comorbidities such as pancreatic insufficiency, diabetes and liver disease. The sweat chloride test, which is the reference standard biomarker of CF diagnosis, was not associated with long-term CF disease progression. These findings demonstrate the potential value of the FIS assay as a prognostic biomarker of long-term CF disease progression, which is particularly useful to inform individuals with rare CFTR variants with unclear clinical consequences about their long-term prognosis. On the other hand, this thesis could not identify predictors that were associated with long-term response to CFTR-modulating drugs in people with CF homozygous for the most prevalent F508del mutation. This indicates that prediction of long-term treatment response remains challenging with the currently available tests and outcome measures in this context, emphasizing the need for alternative outcomes and analysis strategies. In the last part of this thesis, the Q-Life app was developed as a novel personalized electronic patient-reported outcome measure (ePROM) to measure quality of life of people with CF on an individual level. Two observational studies described in this thesis showed that the Q-Life app is a reliable, valid and sensitive ePROM to measure quality of life in a personalized way. The Q-Life app could be a potential new sensitive and relevant outcome measure that can help to optimize personalized treatment of people with CF. As suggested in this thesis, future research in extensive datasets studying various long-term outcomes in real-life settings should reveal at what precision individual disease states and therapeutic responses can be resolved and predicted through a combination of CFTR and non-CFTR dependent individual assessments.

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Report on the p.Ser489X (p.Ser489*) CFTR mutation, a variant with severe associated phenotype and high prevalence in a Quebec French-Canadian cystic fibrosis patient population

Cited by 6 publications

References 12 publications

Personal genome testing in medical education: student experiences with genotyping in the classroom

Personal genome testing in medical education: student experiences with genotyping in the classroom

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

Cystic Fibrosis: a real-world challenge to predict individual outcomes

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