scholarly journals Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations

2010 ◽  
Vol 162 (5) ◽  
pp. 987-992 ◽  
Author(s):  
S E Flanagan ◽  
R R Kapoor ◽  
G Mali ◽  
D Cody ◽  
N Murphy ◽  
...  
Keyword(s):  
Family History ◽  
De Novo ◽  
Clinical Phenotype ◽  
Mutation Screening ◽  
Genetic Diagnosis ◽  
Gene Mutations ◽  
Hyperinsulinemic Hypoglycemia ◽  
Neonatal Hypoglycemia ◽  
Family History Of Diabetes ◽  
History Of

ObjectiveThe phenotype associated with heterozygous HNF4A gene mutations has recently been extended to include diazoxide responsive neonatal hypoglycemia in addition to maturity-onset diabetes of the young (MODY). To date, mutation screening has been limited to patients with a family history consistent with MODY. In this study, we investigated the prevalence of HNF4A mutations in a large cohort of patients with diazoxide responsive hyperinsulinemic hypoglycemia (HH).Subjects and methodsWe sequenced the ABCC8, KCNJ11, GCK, GLUD1, and/or HNF4A genes in 220 patients with HH responsive to diazoxide. The order of genetic testing was dependent upon the clinical phenotype.ResultsA genetic diagnosis was possible for 59/220 (27%) patients. KATP channel mutations were most common (15%) followed by GLUD1 mutations causing hyperinsulinism with hyperammonemia (5.9%), and HNF4A mutations (5%). Seven of the 11 probands with a heterozygous HNF4A mutation did not have a parent affected with diabetes, and four de novo mutations were confirmed. These patients were diagnosed with HI within the first week of life (median age 1 day), and they had increased birth weight (median +2.4 SDS). The duration of diazoxide treatment ranged from 3 months to ongoing at 8 years.ConclusionsIn this large series, HNF4A mutations are the third most common cause of diazoxide responsive HH. We recommend that HNF4A sequencing is considered in all patients with diazoxide responsive HH diagnosed in the first week of life irrespective of a family history of diabetes, once KATP channel mutations have been excluded.

scholarly journals Screening for HNF1B Gene Mutations, in Four People with Typical Diabetes MODY5 Clinical Characteristics

2021 ◽  
Vol 8 (7) ◽  
Author(s):  
Alejandro de Dios ◽  
◽  
Sofia Irene Trobo ◽  
Anette Marianne Prior Gjesing ◽  
Torben Hansen ◽  
...  
Keyword(s):  
Family History ◽  
Genetic Screening ◽  
Clinical Characteristics ◽  
De Novo ◽  
Mutation Screening ◽  
Genetic Diagnosis ◽  
Gene Mutations ◽  
De Novo Mutations ◽  
Family History Of Diabetes ◽  
Bioinformatic Tools

Introduction: people with clinical characteristics of MODY benefit with a correct genetic diagnosis and are often only studied if having family history. In this work there were studied four people selected per their clinical characteristics of genitourinary abnormalities and MODY Diabetes, using the worldwide inclusion criteria for MODY5 except for a family history of diabetes or kidney disease. Methods: gene mutation screening in four people with clinical characteristics of MODY5 in search for alterations in the HNF1B gene with Sanger or NGS sequencing, and bioinformatic tools to analyze the results of the sequences. Results: from four people studied we found three mutations in the HNF1B gene, including a missense mutation previously described and two de novo whole gene deletions. The other person did not present any alteration in that gene even having clinical characteristics. Conclusions: people with clinical characteristics of MODY and having pancreatic, renal, kidney or genital located abnormalities are candidates for genetic screening of HNF1B. Yet, genetic screening of HNF1B should not only be restricted to such people but should also be considered in people without diabetes but having those other characteristics. We suggest also, the study of people even in the absence of family history, given that the possibility of occurrence of de novo mutations is underestimated.

Clinical Characteristics of Pheochromocytoma Patients With Germline Mutations in SDHD

2005 ◽  
Vol 23 (9) ◽  
pp. 1894-1901 ◽  
Author(s):  
Hilde Dannenberg ◽  
Francien H. van Nederveen ◽  
Mustaffa Abbou ◽  
Albert A. Verhofstad ◽  
Paul Komminoth ◽  
...  
Keyword(s):  
Family History ◽  
Mutation Screening ◽  
Gene Mutations ◽  
Neurofibromatosis Type ◽  
Adrenal Tumors ◽  
Molecular Characteristics ◽  
Primary Tumors ◽  
Sdhd Mutation ◽  
Familial Pheochromocytoma ◽  
History Of

Purpose We examined the value of SDHD mutation screening in patients presenting with apparently sporadic and familial pheochromocytoma for the identification of SDHD-related pheochromocytomas. Patients and Methods This retrospective study involved 126 patients with adrenal or extra-adrenal pheochromocytomas, including 24 patients with a family history of multiple endocrine neoplasia 2, von Hippel-Lindau disease, neurofibromatosis type 1, or paraganglioma (PGL). Conformation-dependent gel electrophoresis and sequence determination analysis of germline and tumor DNA were used to identify SDHD alterations. The clinical and molecular characteristics of sporadic and hereditary tumors were compared. We reviewed the literature and compared our results with those from previously published studies. Results Pathogenic germline SDHD mutations were identified in three patients: two (2.0%) of the 102 apparently sporadic pheochromocytoma patients and one patient with a family history of PGL. These patients presented with multifocal disease (two of three multifocal patients) or with a single adrenal tumor (one of 82 patients). In the literature, mutations are mostly found in patients ≤ 35 years of age or presenting with multifocal or extra-adrenal disease. All patients with an SDHD mutation developed extra-adrenal tumors (pheochromocytomas or PGLs) at presentation or during follow-up. Conclusion SDHD gene mutations in patients presenting with apparently sporadic adrenal pheochromocytoma are rare. We recommend SDHD mutation screening for patients presenting with a family history of pheochromocytoma or PGL, multiple tumors, isolated adrenal or extra-adrenal pheochromocytomas, and age ≤ 35 years. Analysis of SDHD can also help to distinguish synchronous primary tumors from abdominal metastases.

Family History of Diabetes Is Associated with Increased Risk of Recurrent DKA in Pediatric Patients in Rhode Island

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1378-P
Author(s):  
JANAKI D. VAKHARIA ◽  
SUNGEETA AGRAWAL ◽  
JANINE BACIC ◽  
LISA S. TOPOR
Keyword(s):  
Family History ◽  
Rhode Island ◽  
Pediatric Patients ◽  
Family History Of Diabetes ◽  
Increased Risk ◽  
History Of

scholarly journals The association between diabetes and thyroid cancer risk: a hospital-based case-control study in China

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Meng Wang ◽  
Wei-Wei Gong ◽  
Feng Lu ◽  
Ru-Ying Hu ◽  
Qing-Fang He ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Family History ◽  
Case Control Study ◽  
Positive Family History ◽  
Case Control ◽  
Diabetes Duration ◽  
Family History Of Diabetes ◽  
Thyroid Cancer Risk ◽  
History Of ◽  
Control Study

Abstract Background Previous studies have indicated inconsistent relationships of diabetes with thyroid cancer risk, yet little is known in China. In this study, we aimed to investigate the associations between diabetes, diabetes duration and the risk of thyroid cancer in Chinese population. Methods A 1:1 matched case-control study was performed between 2015 and 2017 in Zhejiang Province including 2,937 thyroid cancer cases and 2,937 healthy controls. Odds ratios (ORs) with 95 % confidence intervals (CIs) for thyroid cancer were estimated in logistic regression models. Specific effects stratified by age, as well as sex, body mass index (BMI) and family history of diabetes were also examined. Results Overall, neither diabetes (OR = 0.75, 95 % CI: 0.21–2.73) nor diabetes duration (OR = 0.14, 95 % CI: 0.02–1.22 for diabetes duration ≦ 5 years; OR = 2.10, 95 % CI: 0.32–13.94 for diabetes duration > 5 years) was significantly associated with thyroid cancer. In stratified analyses, significant lower risk of thyroid cancer was observed among subjects with diabetes and shorter diabetes duration ( ≦ 5 years), but limited to those who were aged more than 40 years, female, overweight/obese and had positive family history of diabetes. Conclusions Diabetes and shorter diabetes duration were significantly associated with decreased risk of thyroid cancer in individuals characterized by older age, female sex, higher BMI and positive family history of diabetes.

scholarly journals Incidence of diabetes mellitus and associated risk factors in the adult population of the Basque country, Spain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Inés Urrutia ◽  
◽  
Alicia Martín-Nieto ◽  
Rosa Martínez ◽  
J Oriol Casanovas-Marsal ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Family History ◽  
Basque Country ◽  
Adult Population ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Family History Of Diabetes ◽  
History Of ◽  
Incident Cases

AbstractThe aim of this study was to estimate the incidence of diabetes mellitus in the Basque Country and the risk factors involved in the disease by reassessing an adult population after 7 years of follow-up. In the previous prevalence study, 847 people older than 18 years were randomly selected from all over the Basque Country and were invited to answer a medical questionnaire, followed by a physical examination and an oral glucose tolerance test. In the reassessment, the same variables were collected and the resulting cohort comprised 517 individuals of whom 43 had diabetes at baseline. The cumulative incidence of diabetes was 4.64% in 7 years and the raw incidence rate was 6.56 cases/1000 person-years (95%CI: 4.11–9.93). Among the incident cases, 59% were undiagnosed. The most strongly associated markers by univariate analyses were age > 60 years, dyslipidaemia, prediabetes and insulin resistance. We also found association with hypertension, obesity, family history of diabetes and low education level. Multivariate analysis adjusted for age and sex showed that a set of risk factors assessed together (dyslipidaemia, waist-to-hip-ratio and family history of diabetes) had great predictive value (AUC-ROC = 0.899, 95%CI: 0.846–0.953, p = 0.942), which suggests the need for early intervention before the onset of prediabetes.

scholarly journals Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

2021 ◽  
Vol 9 (1) ◽  
pp. e001948
Author(s):  
Marion Denos ◽  
Xiao-Mei Mai ◽  
Bjørn Olav Åsvold ◽  
Elin Pettersen Sørgjerd ◽  
Yue Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Family History ◽  
Genetic Predisposition ◽  
Effect Modification ◽  
P Value ◽  
Family History Of Diabetes ◽  
Increased Risk ◽  
History Of

IntroductionWe sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect modification by family history and genetic predisposition.Research design and methodsThis prospective study included 3574 diabetes-free adults at baseline who participated in the HUNT2 (1995–1997) and HUNT3 (2006–2008) surveys. Serum 25(OH)D levels were determined at baseline and classified as <50 and ≥50 nmol/L. Family history of diabetes was defined as self-reported diabetes among parents and siblings. A Polygenic Risk Score (PRS) for T2DM based on 166 single-nucleotide polymorphisms was generated. Incident T2DM was defined by self-report and/or non-fasting glucose levels greater than 11 mmol/L and serum glutamic acid decarboxylase antibody level of <0.08 antibody index at the follow-up. Multivariable logistic regression models were applied to calculate adjusted ORs with 95% CIs. Effect modification by family history or PRS was assessed by likelihood ratio test (LRT).ResultsOver 11 years of follow-up, 92 (2.6%) participants developed T2DM. A higher risk of incident T2DM was observed in participants with serum 25(OH)D level of<50 nmol/L compared with those of ≥50 nmol/L (OR 1.72, 95% CI 1.03 to 2.86). Level of 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in adults without family history of diabetes (OR 3.87, 95% CI 1.62 to 9.24) but not in those with a family history (OR 0.72, 95% CI 0.32 to 1.62, p value for LRT=0.003). There was no effect modification by PRS (p value for LRT>0.23).ConclusionSerum 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in Norwegian adults. The inverse association was modified by family history of diabetes but not by genetic predisposition to T2DM.

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