scholarly journals Syndromic Monogenic Diabetes Genes Should be Tested in Patients With a Clinical Suspicion of MODY

2021 ◽  
Author(s):  
Kevin Colclough ◽  
Sian Ellard ◽  
Andrew Hattersley ◽  
Kashyap Patel
Keyword(s):  
Genetic Testing ◽  
Clinical Features ◽  
Clinical Care ◽  
Monogenic Diabetes ◽  
Clinical Suspicion ◽  
Genetic Syndrome ◽  
Routine Clinical Care ◽  
Common Causes ◽  
Diabetes Gene ◽  
Diabetes Patients

At present, outside of infancy, genetic testing for monogenic diabetes is typically for mutations in MODY genes that predominantly result in isolated diabetes. Monogenic diabetes syndromes are usually only tested when this is supported by specific syndromic clinical features. It is not known how frequently patients with suspected MODY have a mutation in a monogenic syndromic diabetes gene and thus missed by present testing regimes. We performed<b> </b>genetic testing of 27 monogenic diabetes genes (including 18 associated with syndromic diabetes) for 1280 patients with a clinical suspicion of MODY from routine clinical care that were not suspected of having monogenic syndromic diabetes. We confirmed monogenic diabetes in 297 (23%) patients. Mutations in 7 different syndromic diabetes genes accounted for 19% (95%CI 15-24%) of all monogenic diabetes. The mitochondrial m.3243A>G and mutations in <i>HNF1B</i> were responsible for the majority of mutations in syndromic diabetes genes. They were also the 4<sup>th</sup> and 5<sup>th</sup> most common causes of monogenic diabetes overall. These patients lacked typical features and their diabetes phenotypes overlapped with non-syndromic monogenic diabetes patients. Syndromic monogenic diabetes genes (particularly m.3243A>G and <i>HNF1B</i>) should be routinely tested in patients with suspected MODY that do not have typical features of a genetic syndrome.

scholarly journals Syndromic Monogenic Diabetes Genes Should be Tested in Patients With a Clinical Suspicion of MODY

2021 ◽  
Author(s):  
Kevin Colclough ◽  
Sian Ellard ◽  
Andrew Hattersley ◽  
Kashyap Patel
Keyword(s):  
Genetic Testing ◽  
Clinical Features ◽  
Clinical Care ◽  
Monogenic Diabetes ◽  
Clinical Suspicion ◽  
Genetic Syndrome ◽  
Routine Clinical Care ◽  
Common Causes ◽  
Diabetes Gene ◽  
Diabetes Patients

At present, outside of infancy, genetic testing for monogenic diabetes is typically for mutations in MODY genes that predominantly result in isolated diabetes. Monogenic diabetes syndromes are usually only tested when this is supported by specific syndromic clinical features. It is not known how frequently patients with suspected MODY have a mutation in a monogenic syndromic diabetes gene and thus missed by present testing regimes. We performed<b> </b>genetic testing of 27 monogenic diabetes genes (including 18 associated with syndromic diabetes) for 1280 patients with a clinical suspicion of MODY from routine clinical care that were not suspected of having monogenic syndromic diabetes. We confirmed monogenic diabetes in 297 (23%) patients. Mutations in 7 different syndromic diabetes genes accounted for 19% (95%CI 15-24%) of all monogenic diabetes. The mitochondrial m.3243A>G and mutations in <i>HNF1B</i> were responsible for the majority of mutations in syndromic diabetes genes. They were also the 4<sup>th</sup> and 5<sup>th</sup> most common causes of monogenic diabetes overall. These patients lacked typical features and their diabetes phenotypes overlapped with non-syndromic monogenic diabetes patients. Syndromic monogenic diabetes genes (particularly m.3243A>G and <i>HNF1B</i>) should be routinely tested in patients with suspected MODY that do not have typical features of a genetic syndrome.

scholarly journals Multiplex assay for genetic testing of thrombophilia: a method for routine clinical care

2007 ◽  
Vol 21 (6) ◽  
pp. 349-355 ◽  
Author(s):  
Mónica López ◽  
Pilar Giraldo ◽  
Patricia Alvarez ◽  
R. Cornudella ◽  
Miguel Pocoví ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Clinical Care ◽  
Multiplex Assay ◽  
Routine Clinical Care

scholarly journals Birth weight and diazoxide unresponsiveness strongly predict the likelihood of congenital hyperinsulinism due to a mutation in ABCC8 or KCNJ11

2021 ◽  
Author(s):  
Thomas I Hewat ◽  
Daphne Yau ◽  
Joseph C. S. Jerome ◽  
Thomas W Laver ◽  
Jayne A L Houghton ◽  
...  
Keyword(s):  
Birth Weight ◽  
Clinical Features ◽  
Katp Channel ◽  
Roc Analysis ◽  
Clinical Care ◽  
Area Under The Curve ◽  
Congenital Hyperinsulinism ◽  
Unknown Aetiology ◽  
Routine Clinical Care ◽  
Roc Area

Objective Mutations in the KATP channel genes, ABCC8 and KCNJ11, are the most common cause of congenital hyperinsulinism. The diagnosis of KATP-hyperinsulinism is important for the clinical management of the condition. We aimed to determine the clinical features that help to identify KATP-hyperinsulinism at diagnosis. Design We studied 761 individuals with KATP-hyperinsulinism and 862 probands with hyperinsulinism of unknown aetiology diagnosed before 6 months of age. All were referred as part of routine clinical care. Methods We compared the clinical features of KATP-hyperinsulinism and unknown hyperinsulinism cases. We performed logistic regression and ROC analysis to identify the features that predict KATP-hyperinsulinism. Results Higher birth weight, diazoxide unresponsiveness and diagnosis in the first week of life were independently associated with KATP-hyperinsulinism (adjusted Odds Ratio 4.5 (95% CI, 3.4-5.9), 0.09 (0.06-0.13) and 3.3 (2.0- 5.0) respectively). Birth weight and diazoxide unresponsiveness were additive and highly discriminatory for identifying KATP-hyperinsulinism (ROC area under the curve for birth weight 0.80, diazoxide responsiveness 0.77, and together 0.88, 95% CI 0.85-0.90). 86% born large for gestation and 78% born appropriate for gestation who did not respond to diazoxide treatment had KATP-hyperinsulinism. In contrast, of those individuals born small for gestation, none who were diazoxide responsive and only 4% of those who were diazoxide unresponsive had KATP-hyperinsulinism. Conclusions Individuals with hyperinsulinism born appropriate or large for gestation and unresponsive to diazoxide treatment are most likely to have an ABCC8 or KCNJ11 mutation. These patients should be prioritised for genetic testing for KATP channel genes.

scholarly journals Gene Panel Sequencing of Patients With Monogenic Diabetes Brings to Light Genes Typically Associated With Syndromic Presentations

2021 ◽  
Author(s):  
Cécile Saint-Martin ◽  
Delphine Bouvet ◽  
Mathilda Bastide ◽  
Christine Bellanné-Chantelot
Keyword(s):  
Hearing Loss ◽  
Genetic Testing ◽  
Wolfram Syndrome ◽  
Monogenic Diabetes ◽  
Gene Panel ◽  
Genetic Syndrome ◽  
The Third ◽  
Gene Panel Sequencing ◽  
Inherited Diabetes ◽  
Panel Sequencing

Gene panel sequencing (NGS) offers the possibility to analyze rare forms of monogenic diabetes (MgD). To that end, 18 genes were analyzed in 1676 patients referred for MODY genetic testing. <p>Among the 307 patients with a molecular diagnosis of MgD, 55 (17.9%) were mutated in a gene associated with a genetic syndrome. Eight percent (n=25) of the patients with mutations carried the m.3243A>G variant associated with MIDD (Maternally inherited diabetes and deafness). At time of referral very little had reported hearing loss or any other element of the typical syndromic presentation. Six percent of the patients were mutated in <i>HNF1B</i> even though the typical extra-pancreatic features were not known at time of referral. Surprisingly the third most prominent etiology in these rare forms was the <i>WFS1</i> gene accounting for 2.9% of the patients with pathogenic mutations (n=9). None of them depicted a Wolfram syndrome presentation even though some features were reported in 6/9 patients. </p> <p>Restricting the analysis of certain genes to patients with the respective specific phenotypes would miss out those with partial presentations. These results therefore underlie the undisputable benefit of NGS strategies even though the situation implies cascade consequences both for the molecular biologist and the clinician.</p>

scholarly journals Gene Panel Sequencing of Patients With Monogenic Diabetes Brings to Light Genes Typically Associated With Syndromic Presentations

2021 ◽  
Author(s):  
Cécile Saint-Martin ◽  
Delphine Bouvet ◽  
Mathilda Bastide ◽  
Christine Bellanné-Chantelot
Keyword(s):  
Hearing Loss ◽  
Genetic Testing ◽  
Wolfram Syndrome ◽  
Monogenic Diabetes ◽  
Gene Panel ◽  
Genetic Syndrome ◽  
The Third ◽  
Gene Panel Sequencing ◽  
Inherited Diabetes ◽  
Panel Sequencing

Gene panel sequencing (NGS) offers the possibility to analyze rare forms of monogenic diabetes (MgD). To that end, 18 genes were analyzed in 1676 patients referred for MODY genetic testing. <p>Among the 307 patients with a molecular diagnosis of MgD, 55 (17.9%) were mutated in a gene associated with a genetic syndrome. Eight percent (n=25) of the patients with mutations carried the m.3243A>G variant associated with MIDD (Maternally inherited diabetes and deafness). At time of referral very little had reported hearing loss or any other element of the typical syndromic presentation. Six percent of the patients were mutated in <i>HNF1B</i> even though the typical extra-pancreatic features were not known at time of referral. Surprisingly the third most prominent etiology in these rare forms was the <i>WFS1</i> gene accounting for 2.9% of the patients with pathogenic mutations (n=9). None of them depicted a Wolfram syndrome presentation even though some features were reported in 6/9 patients. </p> <p>Restricting the analysis of certain genes to patients with the respective specific phenotypes would miss out those with partial presentations. These results therefore underlie the undisputable benefit of NGS strategies even though the situation implies cascade consequences both for the molecular biologist and the clinician.</p>

Reconsidering NMIHBA Core Features: Macrocephaly Is Not a So Unusual Sign in PRUNE1-Related Encephalopathy

2020 ◽  
Author(s):  
Roberta Battini ◽  
Enrico Bertini ◽  
Roberta Milone ◽  
Chiara Aiello ◽  
Rosa Pasquariello ◽  
...  
Keyword(s):  
Nervous System ◽  
Differential Diagnosis ◽  
Clinical Features ◽  
Neurodevelopmental Disorder ◽  
Recurrent Mutation ◽  
Clinical Suspicion ◽  
Alexander Disease ◽  
Brain Anomalies ◽  
Progressive Encephalopathy ◽  
Core Features

Abstract PRUNE1-related disorders manifest as severe neurodevelopmental conditions associated with neurodegeneration, implying a differential diagnosis at birth with static encephalopathies, and later with those manifesting progressive brain damage with the involvement of both the central and the peripheral nervous system.Here we report on another patient with PRUNE1 (p.Asp106Asn) recurrent mutation, whose leukodystrophy, inferior olives hyperintensity, and macrocephaly led to the misleading clinical suspicion of Alexander disease. Clinical features, together with other recent descriptions, suggest avoiding the term “microcephaly” in defining this disorder that could be renamed “neurodevelopmental disorder with progressive encephalopathy, hypotonia, and variable brain anomalies” (NPEHBA).

Treatment of painful bone metastases in prostate and breast cancer patients with the therapeutic radiopharmaceutical rhenium-188-HEDP

2016 ◽  
Vol 55 (05) ◽  
pp. 188-195 ◽  
Author(s):  
Floor Overbeek ◽  
John de Klerk ◽  
Pieternel Pasker-de Jong ◽  
Alexandra van den Berk ◽  
Rob ter Heine ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Clinical Benefit ◽  
Response Rate ◽  
Clinical Care ◽  
Pain Response ◽  
Pain Palliation ◽  
Breast Cancer Patients ◽  
Routine Clinical Care ◽  
Painful Bone Metastases

Summary Aim: Rhenium-188-HEDP (188Re-HEDP) is an effective radiopharmaceutical for the palliative treatment of osteoblastic bone metastases. However, only limited data on its routine use are available and its effect on quality of life (QoL) has not been studied. Therefore, we evaluated the clinical benefit of 188Re-HEDP in routine clinical care. Patients and methods: Prostate or breast cancer patients with painful bone metastases receiving 188Re-HEDP as a routine clinical procedure were eligible for evaluation. Clinical benefit was assessed in terms of efficacy and toxicity. Pain palliation and QoL were monitored using the visual analogue scale (VAS), corrected for opioid intake, and the EORTC QLQ-C30 Global health status/QoL-scale. Thrombocyte and leukocyte nadirs were used to assess haematological toxicity. Results: 45 and 47 patients were evaluable for pain palliation and QoL, respectively. After a single injection of 188Re-HEDP, the overall pain response rate was 69% and mean VAS-scores decreased relevantly and significantly (p < 0.05). Repeated treatment resulted in similar pain response. The overall QoL response rate was 68% and mean Global health status/QoL-scores increased relevantly and significantly. Haematological side effects were mild and transient. Conclusion: The clinically relevant response on pain and quality of life and the limited adverse events prove clinical benefit of treatment with 188Re-HEDP and support its use in routine clinical care. Its effectiveness appears comparable to that of external beam radiotherapy.

Interpersonal Psychotherapy for the Treatment of Eating Disorders

2010 ◽  
pp. 347-372 ◽  
Author(s):  
Marian Tanofsky-Kraff ◽  
Denise E. Wilfley
Keyword(s):  
Anorexia Nervosa ◽  
Clinical Care ◽  
Interpersonal Psychotherapy ◽  
Future Research ◽  
Cognitive Behavior ◽  
Research Directions ◽  
Routine Clinical Care ◽  
Interpersonal Factors ◽  
Future Research Directions

Interpersonal psychotherapy (IPT) is a focused, time-limited treatment that targets interpersonal problem(s) associated with the onset and/or maintenance of EDs. IPT is supported by substantial empirical evidence documenting the role of interpersonal factors in the onset and maintenance of EDs. IPT is a viable alternative to cognitive behavior therapy for the treatment of bulimia nervosa and binge eating disorder. The effectiveness of IPT for the treatment of anorexia nervosa requires further investigation. The utility of IPT for the prevention of obesity is currently being explored. Future research directions include enhancing the delivery of IPT for EDs, increasing the availability of IPT in routine clinical care settings, exploring IPT adolescent and parent–child adaptations, and developing IPT for the prevention of eating and weight-related problems that may promote full-syndrome EDs or obesity.

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