A decade of molecular genetic testing for MODY: a retrospective study of utilization in The Netherlands

Weinreich, S.; Bosma, A. R.; Henneman, Lidewij; Rigter, Tessel; Spruijt, Carla M J; Grimbergen, Anneliese J E M A; Breuning, Martijn H.; Koning, Eelco J.P. de; Losekoot, Monique; Cornel, Martina C.

doi:10.1038/ejhg.2014.59

Cited by 23 publications

(20 citation statements)

References 19 publications

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“…As genetic testing for MODY increased over the span of the study, more cases were discovered and the average age of referral for testing increased in HNF1A -MODY cases (25.7 during 2003–2004 to 29.2 during 2009–2010, p=0.022). (26) These examples of centralized monogenic diabetes testing facilities allow relatively comprehensive population studies regarding the patient characteristics, physician criteria, and testing outcome dynamics of MODY diagnosis.…”

Section: Mody Epidemiology Studiesmentioning

confidence: 99%

Undiagnosed MODY: Time for Action

2015

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Maturity-Onset Diabetes of the Young (MODY) is a monogenic form of diabetes that accounts for at least 1% of all cases of diabetes mellitus. MODY classically presents as non-insulin requiring diabetes in lean individuals younger than 25 with evidence of autosomal dominant inheritance, but these criteria do not capture all cases and can also overlap with other diabetes types. Genetic diagnosis of MODY is important for selecting the right treatment, yet ~95% of MODY cases in the U.S. are misdiagnosed. MODY prevalence and characteristics have been well-studied in some populations, such as the UK and Norway, while other ethnicities, like African and Latino, need much more study. Emerging next-generation sequencing methods are making more widespread study and clinical diagnosis increasingly feasible. This review will cover the current epidemiological studies of MODY and barriers and opportunities for moving toward a goal of access to an appropriate diagnosis for all affected individuals.

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Section: Mody Epidemiology Studiesmentioning

confidence: 99%

Undiagnosed MODY: Time for Action

2015

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“…In The Netherlands, for example, it was estimated that there should be ∼20,000 MODY patients [6]; however, until 2012, only 502 HNF1A, GCK and HNF4A patients were genetically diagnosed [7], and it is unknown how many patients were clinically diagnosed. A large number of patients have not been tested, even though genetic identification of MODY may have several benefits.…”

Section: Introductionmentioning

confidence: 99%

Current and Best Practices of Genetic Testing for Maturity Onset Diabetes of the Young: Views of Professional Experts

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Weinreich

Bosma

et al. 2014

Public Health Genomics

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Aims: Currently, many patients with maturity onset diabetes of the young (MODY) are undiagnosed or misdiagnosed with type 1 or 2 diabetes. This study aims to assess professional experts' views on factors which may influence the current practice of genetic testing for MODY and to explore next steps toward best practice. Methods: Twelve semistructured interviews were conducted with professional experts. These experts included physicians with potential or actual experience with genetic testing for MODY, representatives of (para)medical professional associations and a staff member of a diabetes patients' organization. Results: Participants differed in their valuation of genetic testing for MODY. While most considered the test useful, not all were convinced of its clinical utility. Other factors mentioned to influence current practice were: (perceived lack of) possibilities for treatment and prevention, patients' perspectives and perceived barriers, such as costs and a lack of knowledge and awareness. Participants agreed that guidelines would be helpful to facilitate expedient testing. Conclusions: This study identified next steps that should be taken to improve genetic diagnosis and care for patients with MODY. Besides the development of a consensus guideline, other suggestions included more education of healthcare professionals, a clearer allocation of responsibilities with regard to genetic testing for MODY and further research.

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“…From a retrospective study in the UK population (between 1996 and 2009), the prevalence of MODY was reported to be approximately 100 cases per 10 6 population, with a large variability among UK provinces . Other estimates from population‐based childhood diabetes registries range between 2.5–5 cases per 100 000 in several European countries and 2.1 cases per 100 000 in American children from the SEARCH for Diabetes in Youth Study . A high frequency (>20 %) of clinically suspected MODY was reported among patients with T2D younger than 25 years of age in south India, but no genetic characterization was performed.…”

Section: Genetic Subtypes and Clinical Spectrum Of Monogenic Diabetesmentioning

confidence: 99%

Monogenic diabetes: Implementation of translational genomic research towards precision medicine

Vaxillaire

Froguel

2016

Journal of Diabetes

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Various forms of early-onset non-autoimmune diabetes are recognized as monogenic diseases, each subtype being caused by a single highly penetrant gene defect at the individual level. Monogenic diabetes (MD) is clinically and genetically heterogeneous, including maturity-onset diabetes of the young (MODY), infancy-onset and neonatal diabetes mellitus, which are characterized by functional defects of insulin-producing pancreatic -cells and hyperglycemia early in life. Depending on the genetic cause, MD differs in ages at diabetes onset, the severity of hyperglycemia, long-term diabetic complications and extra-pancreatic manifestations. In this review, we discuss the many challenges of molecular genetic diagnosis of MD in the face of a substantial genetic heterogeneity; as well as the clinical benefit and cost-effectiveness of an early genetic diagnosis as demonstrated by simulation models based on lifetime complications and treatment costs. We also discuss striking examples of proof-of-concept of genomic medicine, which enabled to remarkably improve patients' care and long-term evolution. Recent advances in genome editing and pluripotent stem-cell reprogramming technologies provide new opportunities for in vitro diabetes modelling and the discovery of novel drug targets and cell-based diabetes therapies. A review of these future directions makes the case for exciting translational research for further understanding early-onset diabetes pathophysiology. Keywords:Diabetes, Genetics, Genomic medicine, Insulin secretion, Monogenic diabetes, MODY, Mutation, Next-generation sequencing, pancreatic -cell.This article is protected by copyright. All rights reserved. Genetic subtypes and clinical spectrum of monogenic diabetesMonogenic diabetes (MD) is caused by a rare single-gene defect that strongly contributes to the disease phenotype without or not much environmental contribution (meaning that is each individual DNA mutation or genome structural abnormality has a high or almost complete penetrance).1 MD encompasses a broad spectrum of clinically and genetically highly heterogeneous forms of nonautoimmune diabetes, which are mainly characterized by functional defects of pancreatic -cells resulting in insulin deficiency and moderate to severe hyperglycemia early in life. 1,2 MD includes maturity-onset diabetes of the young (MODY), early-infancy onset and neonatal diabetes mellitus (NDM), and many rare forms of atypical diabetes. [1][2][3] Decades of genetic and clinical research to decipher etiological mechanisms underlying MODY, NDM and early-infancy diabetes led to identify major genes and molecular pathways relevant to -cell physiology, that allowed to better understand the sustained genetic and clinical heterogeneity among the different MD subtypes in young people. MODY subtypesMODY usually presents in lean young individuals before age 25-30 years, as a dominantly inherited familial form of diabetes, and it may account for at least ~1-2% of all cases with type 2 diabetes. 4,5Epidemiology of MODY. Although M...

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A decade of molecular genetic testing for MODY: a retrospective study of utilization in The Netherlands

Cited by 23 publications

References 19 publications

Undiagnosed MODY: Time for Action

Undiagnosed MODY: Time for Action

Current and Best Practices of Genetic Testing for Maturity Onset Diabetes of the Young: Views of Professional Experts

Monogenic diabetes: Implementation of translational genomic research towards precision medicine

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