Maturity Onset Diabetes of the Young is Not Necessarily Associated with Autosomal Inheritance: Case Description of a De Novo HFN1A Mutation

Salzano, Giuseppina; Passanisi, Stefano; Mammì, Corrado; Priolo, Manuela; Pintomalli, Letizia; Caminiti, Lucia; Messina, Maria Francesca; Pajno, Giovanni Battista; Lombardo, Fortunato

doi:10.1007/s13300-019-0633-3

Cited by 3 publications

(4 citation statements)

References 36 publications

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“…[ 29 ] As for FHD, a powerful discriminated parameter for MODY, underestimation of self-report, de novo variants and a high proportion of FHD in T2DM, would limit its role in identifying MODY from T2DM. Furthermore, epidemiological studies have demonstrated that de novo mutations of the major MODY genes could be more frequent than what was previously assumed, [ 35 ] Stanik et al [ 36 ] described 11 de novo mutations of GCK , HNF1A , and HNF4A in 150 probands fulfilled all MODY criteria. In addition, potential biomarkers such as high-sensitivity C-reactive protein and urine C-peptide creatinine ratio have shown promising results in specifically separating the most common types of MODY from other subtypes.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of maturity-onset diabetes of the young in phenotypic type 2 diabetes in young adults: a nationwide, multi-center, cross-sectional survey in China

Chen

Zhao

et al. 2023

Chinese Medical Journal

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Background:Maturity-onset diabetes of the young (MODY) is the most common monogenic diabetes. The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes (T2DM) among Chinese young adults.Methods:From April 2015 to October 2017, this cross-sectional study involved 2429 consecutive patients from 46 hospitals in China, newly diagnosed between 15 years and 45 years, with T2DM phenotype and negative for standardized glutamic acid decarboxylase antibody at the core laboratory. Sequencing using a custom monogenic diabetes gene panel was performed, and variants of 14 MODY genes were interpreted as per current guidelines.Results:The survey determined 18 patients having genetic variants causing MODY (6 HNF1A, 5 GCK, 3 HNF4A, 2 INS, 1 PDX1, and 1 PAX4). The prevalence of MODY was 0.74% (95% confidence interval [CI]: 0.40–1.08%). The clinical characteristics of MODY patients were not specific, 72.2% (13/18) of them were diagnosed after 35 years, 47.1% (8/17) had metabolic syndrome, and only 38.9% (7/18) had a family history of diabetes. No significant difference in manifestations except for hemoglobin A1c levels was found between MODY and non-MODY patients.Conclusion:The prevalence of MODY in young adults with phenotypic T2DM was 0.74%, among which HNF1A-, GCK-, and HNF4A-MODY were the most common subtypes. Clinical features played a limited role in the recognition of MODY.

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Section: Discussionmentioning

confidence: 99%

Prevalence of maturity-onset diabetes of the young in phenotypic type 2 diabetes in young adults: a nationwide, multi-center, cross-sectional survey in China

Chen

Zhao

et al. 2023

Chinese Medical Journal

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“…As a case of autosomal dominant inherited disease, MODY3 patients usually have a family history of diabetes ( 9 , 27 , 28 ). Some studies suggest that the probability of a family history of MODY3 is more than 20 times higher than that of T1D ( 29 ). However, some MODY patients may lack a family history of diabetes, possibly due to the following factors ( 1 ): the probability of new HNF1A-MODY mutations may be more frequent than expected, and (2) the family members of the patients were not diagnosed because of mild clinical symptoms and signs ( 29 , 30 ).…”

Section: Association Between Hnf1a Polymorphism and Mody3mentioning

confidence: 99%

HNF1A：From Monogenic Diabetes to Type 2 Diabetes and Gestational Diabetes Mellitus

Jiang

Sun

2022

Front. Endocrinol.

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Diabetes, a disease characterized by hyperglycemia, has a serious impact on the lives and families of patients as well as on society. Diabetes is a group of highly heterogeneous metabolic diseases that can be classified as type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM), or other according to the etiology. The clinical manifestations are more or less similar among the different types of diabetes, and each type is highly heterogeneous due to different pathogenic factors. Therefore, distinguishing between various types of diabetes and defining their subtypes are major challenges hindering the precise treatment of the disease. T2D is the main type of diabetes in humans as well as the most heterogeneous. Fortunately, some studies have shown that variants of certain genes involved in monogenic diabetes also increase the risk of T2D. We hope this finding will enable breakthroughs regarding the pathogenesis of T2D and facilitate personalized treatment of the disease by exploring the function of the signal genes involved. Hepatocyte nuclear factor 1 homeobox A (HNF1α) is widely expressed in pancreatic β cells, the liver, the intestines, and other organs. HNF1α is highly polymorphic, but lacks a mutation hot spot. Mutations can be found at any site of the gene. Some single nucleotide polymorphisms (SNPs) cause maturity-onset diabetes of the young type 3 (MODY3) while some others do not cause MODY3 but increase the susceptibility to T2D or GDM. The phenotypes of MODY3 caused by different SNPs also differ. MODY3 is among the most common types of MODY, which is a form of monogenic diabetes mellitus caused by a single gene mutation. Both T2D and GDM are multifactorial diseases caused by both genetic and environmental factors. Different types of diabetes mellitus have different clinical phenotypes and treatments. This review focuses on HNF1α gene polymorphisms, HNF1A-MODY3, HNF1A-associated T2D and GDM, and the related pathogenesis and treatment methods. We hope this review will provide a valuable reference for the precise and individualized treatment of diabetes caused by abnormal HNF1α by summarizing the clinical heterogeneity of blood glucose abnormalities caused by HNF1α mutation.

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“…No family history of diabetes was present. Genetic investigations revealed a de novo missense mutation in the exon 3 of HFN1A gene (HFN1A-c.709A > G) [8]. Other patterns of clinical presentation varied from hypoglycaemic episodes to hyperglycaemia.…”

Section: Hfn1a-modymentioning

confidence: 99%

“…age of onset, clinical features, type of treatment) [5]. Although the traditional criteria for MODY include a family history of diabetes, sporadic de novo mutations in a number of causative genes have been reported [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Clinical and genetic features of maturity-onset diabetes of the young in pediatric patients: a 12-year monocentric experience

Passanisi

Salzano

Lombardo

2021

Diabetol Metab Syndr

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Background A retrospective observational study was conducted to assess the prevalence of maturity onset diabetes of the young (MODY) in a large paediatric population of Southern Italy newly diagnosed with diabetes. Clinical and genetic features of the identified MODY patients were also described. Methods Genetic testing was performed in children and adolescents newly diagnosed with diabetes who presented autoantibody negativity and fasting C-peptide levels ≥ 0.8 ng/mL. Patients with a low insulin daily dose and optimal glycaemic control after two years from diabetes onset were also investigated for monogenic diabetes, regardless of their autoimmunity status and/or C-peptide levels. Results A prevalence of 6.5% of MODY was found. In particular, glucokinase-MODY was the most common type of MODY. The mean age at diagnosis was 9.1 years. Clinical presentation and biochemical data were heterogeneous also among patients belonging to the same MODY group. Conclusions We found a relatively high prevalence of MODY among paediatric patients with a new diagnosis of diabetes in comparison to literature data. Our findings highlight that a more detailed clinical evaluation along with easier and less expensive approachability to genetic testing may allow diagnosing an increasing number of MODY cases. A correct, prompt diagnosis is crucial to choose the most appropriate treatment and offer adequate genetic counselling.

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Maturity Onset Diabetes of the Young is Not Necessarily Associated with Autosomal Inheritance: Case Description of a De Novo HFN1A Mutation

Cited by 3 publications

References 36 publications

Prevalence of maturity-onset diabetes of the young in phenotypic type 2 diabetes in young adults: a nationwide, multi-center, cross-sectional survey in China

Prevalence of maturity-onset diabetes of the young in phenotypic type 2 diabetes in young adults: a nationwide, multi-center, cross-sectional survey in China

HNF1A：From Monogenic Diabetes to Type 2 Diabetes and Gestational Diabetes Mellitus

Clinical and genetic features of maturity-onset diabetes of the young in pediatric patients: a 12-year monocentric experience

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