Anne-Marie Laberge

Bio: Anne-Marie Laberge is an academic researcher from Université de Montréal. The author has contributed to research in topics: Health care & Genetic testing. The author has an hindex of 18, co-authored 61 publications receiving 1069 citations. Previous affiliations of Anne-Marie Laberge include Centre Hospitalier Universitaire Sainte-Justine & McGill University.

Population history and its impact on medical genetics in Quebec.

Abstract: Knowledge of the genetic demography of Quebec is useful for gene mapping, diagnosis, treatment, community genetics and public health. The French-Canadian population of Quebec, currently about 6 million people, descends from about 8500 French settlers who arrived in Nouvelle-France between 1608 and 1759. The migrations of those settlers and their descendants led to a series of regional founder effects, reflected in the geographical distribution of genetic diseases in Quebec. This review describes elements of population history and clinical genetics pertinent to the treatment of French Canadians and other population groups from Quebec and summarizes the cardinal features of over 30 conditions reported in French Canadians. Some were discovered in French Canadians, such as autosomal recessive ataxia of the Charlevoix-Saguenay (MIM 270550), agenesis of corpus callosum and peripheral neuropathy (MIM 218000) and French-Canadian-type Leigh syndrome (MIM 220111). Other conditions are particularly frequent or have special genetic characteristics in French Canadians, including oculopharyngeal muscular dystrophy, hepatorenal tyrosinaemia, cystic fibrosis, Leber hereditary optic neuropathy and familial hypercholesterolaemia. Three genetic diseases of Quebec First Nations children are also discussed: Cree encephalitis (MIM 608505), Cree leukoencephalopathy (MIM 603896) and North American Indian childhood cirrhosis (MIM 604901).

The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists

Abstract: Purpose and scope The aim of this Position Statement is to provide recommendations for Canadian medical geneticists, clinical laboratory geneticists, genetic counsellors and other physicians regarding the use of genome-wide sequencing of germline DNA in the context of clinical genetic diagnosis. This statement has been developed to facilitate the clinical translation and development of best practices for clinical genome-wide sequencing for genetic diagnosis of monogenic diseases in Canada; it does not address the clinical application of this technology in other fields such as molecular investigation of cancer or for population screening of healthy individuals. Methods of statement development Two multidisciplinary groups consisting of medical geneticists, clinical laboratory geneticists, genetic counsellors, ethicists, lawyers and genetic researchers were assembled to review existing literature and guidelines on genome-wide sequencing for clinical genetic diagnosis in the context of monogenic diseases, and to make recommendations relevant to the Canadian context. The statement was circulated for comment to the Canadian College of Medical Geneticists (CCMG) membership-at-large and, following incorporation of feedback, approved by the CCMG Board of Directors. The CCMG is a Canadian organisation responsible for certifying medical geneticists and clinical laboratory geneticists, and for establishing professional and ethical standards for clinical genetics services in Canada. Results and conclusions Recommendations include (1) clinical genome-wide sequencing is an appropriate approach in the diagnostic assessment of a patient for whom there is suspicion of a significant monogenic disease that is associated with a high degree of genetic heterogeneity, or where specific genetic tests have failed to provide a diagnosis; (2) until the benefits of reporting incidental findings are established, we do not endorse the intentional clinical analysis of disease-associated genes other than those linked to the primary indication; and (3) clinicians should provide genetic counselling and obtain informed consent prior to undertaking clinical genome-wide sequencing. Counselling should include discussion of the limitations of testing, likelihood and implications of diagnosis and incidental findings, and the potential need for further analysis to facilitate clinical interpretation, including studies performed in a research setting. These recommendations will be routinely re-evaluated as knowledge of diagnostic and clinical utility of clinical genome-wide sequencing improves. While the document was developed to direct practice in Canada, the applicability of the statement is broader and will be of interest to clinicians and health jurisdictions internationally.

Genetics in health care: an overview of current and emerging models.

Abstract: Background: With advances in genetic and genomic medicine, the optimal integration of genetic services into the health care system remains of major concern in many countries. Objectives: To review the current organisation of genetic services, mostly in Europe, North America and Australia, explore emerging service delivery models, and probe challenges inherent in the transition process. Methods: We conducted a literature review of genetics in clinical practice: testing, diagnosis, counselling, and treatment. We examined the basic structures of genetic services, examples of integrated networks, and existing professional resources. We investigated services belonging traditionally in medical genetics as well as those developed for more common diseases. Results: Multidisciplinary specialist clinics and coordinated services appeared to be key to delivering proper care in rare genetic disorders. For oncogenetics, neurogenetics and cardiogenetics, interprofessional collaboration be

BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells

Abstract: The transcription factor BCL11B is essential for development of the nervous and the immune system, and Bcl11b deficiency results in structural brain defects, reduced learning capacity, and impaired immune cell development in mice However, the precise role of BCL11B in humans is largely unexplored, except for a single patient with a BCL11B missense mutation, affected by multisystem anomalies and profound immune deficiency Using massively parallel sequencing we identified 13 patients bearing heterozygous germline alterations in BCL11B Notably, all of them are affected by global developmental delay with speech impairment and intellectual disability; however, none displayed overt clinical signs of immune deficiency Six frameshift mutations, two nonsense mutations, one missense mutation, and two chromosomal rearrangements resulting in diminished BCL11B expression, arose de novo A further frameshift mutation was transmitted from a similarly affected mother Interestingly, the most severely affected patient harbours a missense mutation within a zinc-finger domain of BCL11B, probably affecting the DNA-binding structural interface, similar to the recently published patient Furthermore, the most C-terminally located premature termination codon mutation fails to rescue the progenitor cell proliferation defect in hippocampal slice cultures from Bcl11b-deficient mice Concerning the role of BCL11B in the immune system, extensive immune phenotyping of our patients revealed alterations in the T cell compartment and lack of peripheral type 2 innate lymphoid cells (ILC2s), consistent with the findings described in Bcl11b-deficient mice Unsupervised analysis of 102 T lymphocyte subpopulations showed that the patients clearly cluster apart from healthy children, further supporting the common aetiology of the disorder Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay In addition, we suggest that missense mutations affecting specific sites within zinc-finger domains might result in distinct and more severe clinical outcomes

Debating Clinical Utility

Abstract: The clinical utility of genetic tests is determined by the outcomes following test use. Like other measures of value, it is often contested. Stakeholders may have different views about benefits and risks and about the importance of social versus health outcomes. They also commonly disagree about the evidence needed to determine whether a test is effective in achieving a specific outcome. Questions may be presented as factual disagreements, when they are actually debates about what information matters or how facts should be interpreted and used in clinical decision-making. Defining the different issues at stake is therefore an important element of policy-making. Key issues include evidence standards for test use, and in particular, the circumstances under which prospective controlled data should be required, as well as evidence on feasibility, cost and equitable delivery of testing; the goals of population-based screening programs, and in particular, the role of social outcomes in evaluating test value; and the appropriate uses and funding of tests that inform non-medical actions. Addressing each of these issues requires attention to stakeholder values and methods for effective deliberation that incorporate consumer as well as health professional perspectives.

Regression Diagnostics: Identifying Influential Data and Sources of Collinearity

Abstract: 1. Introduction and Overview. 2. Detecting Influential Observations and Outliers. 3. Detecting and Assessing Collinearity. 4. Applications and Remedies. 5. Research Issues and Directions for Extensions. Bibliography. Author Index. Subject Index.

Research Design: Qualitative, Quantitative, and Mixed Method Approaches

Abstract: หนงสอเรอง การออกแบบการวจย: วธการวจยเชงคณภาพ วธการวจยเชงปรมาณ และวธการวจยแบบผสม (Research Design: Qualitative, Quantitative, and Mixed Method Approaches) เปนหนงสอทเรยบเรยงเพออธบายเกยวกบความแตกตางของกระบวนทศนการวจยทง 2 แบบ ไดแก การวจย เชงปรมาณ และการวจยเชงคณภาพ และความจำเปนของประเดนปญหาการวจยทตองนำกระบวนทศนทง 2 มารวมกนหาขอคนพบเพอนำไปสผลการวจยทสามารถนำผลการวจยไปใชประโยชนไดอยางจรงมากยงขน เรยกวา “การวจยแบบผสมผสาน” ซงเปนหนงสอทอธบายวธการวจยทง 2 ประเภทไดอยางชดเจน และการรวมกนของกระบวนทศนการวจยทง 2 แบบอยางลงตว

2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC)

Abstract: ACC : American College of Cardiology ACE : angiotensin-converting enzyme ACS : acute coronary syndrome AF : atrial fibrillation AGNES : Arrhythmia Genetics in the Netherlands AHA : American Heart Association AMIOVIRT : AMIOdarone Versus Implantable cardioverter-defibrillator: