An Atypical HNF4A Mutation Which Does Not Conform to the Classic Presentation of HNF4A-MODY

Spiro, Andrew J.; Vu, Katherine; Warnock, Alicia

doi:10.1155/2018/1560472

Cited by 6 publications

(5 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This phenotypic variability and incomplete penetrance have been also described in HNF4A/MODY [ 28 , 29 ] and were found in our clinical experience too (unpublished data).…”

Section: Discussionsupporting

confidence: 84%

“…Some of these loci may exert their effect at the level of the beta-cell, enhancing the insulin secretion deficit caused by HNF1A mutations; others may influence the onset of diabetes by affecting the amount of insulin that peripheral tissues require to maintain glycemia at the normal level [25]. This phenotypic variability and incomplete penetrance have been also described in HNF4A/MODY [28,29] and were found in our clinical experience too (unpublished data).…”

Section: Discussionsupporting

confidence: 75%

See 1 more Smart Citation

NGS Analysis Revealed Digenic Heterozygous GCK and HNF1A Variants in a Child with Mild Hyperglycemia: A Case Report

et al. 2021

View full text Add to dashboard Cite

Monogenic diabetes (MD) represents a heterogeneous group of disorders whose most frequent form is maturity-onset diabetes of the young (MODY). MD is predominantly caused by a mutation in a single gene. We report a case of a female patient with suspected MD and a positive family history for diabetes and obesity. In this patient, two gene variants have been identified by next-generation sequencing (NGS): one in the Glucokinase (GCK) gene reported in the Human Gene Mutation Database (HGMD) and in the literature associated with GCK/MODY, and the other in the hepatocyte nuclear factor 1A (HNF1A) gene not previously described. The GCK variant was also identified in the hyperglycemic father, whereas the HNF1A variant was present in the mother. This new case of digenic GCK/HNF1A variants identified in a hyperglycemic subject, evidences the importance of NGS analysis in patients with suspected MD. In fact, this methodology will allow us to both increase the number of diagnoses and to identify mutations in more than one gene, with a better understanding of the genetic cause, and the clinical course, of the disease.

show abstract

“…This phenotypic variability and incomplete penetrance have been also described in HNF4A/MODY [ 28 , 29 ] and were found in our clinical experience too (unpublished data).…”

Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 75%

NGS Analysis Revealed Digenic Heterozygous GCK and HNF1A Variants in a Child with Mild Hyperglycemia: A Case Report

et al. 2021

View full text Add to dashboard Cite

show abstract

“…This gene encodes a transcription factor. Its symptoms is similar to the MODY3 [ 13 ]. Variants in INS , encoding a protein regulating crucial metabolic processes [ 14 ] lead to misfolding of insulin and defective trafficking.…”

Section: Discussionmentioning

confidence: 99%

Causal variants in Maturity Onset Diabetes of the Young (MODY) – A systematic review

Rafique

Mir

Saqib³

et al. 2021

BMC Endocr Disord

View full text Add to dashboard Cite

Background Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant type of diabetes. Pathogenic variants in fourteen genes are reported as causes of MODY. Its symptoms overlap with type 1 and type 2 diabetes. Reviews for clinical characteristics, diagnosis and treatments are available but a comprehensive list of genetic variants, is lacking. Therefore this study was designed to collect all the causal variants involved in MODY, reported to date. Methods We searched PubMed from its date of inception to December 2019. The search terms we used included disease names and name of all the known genes involved. The ClinVar database was also searched for causal variants in the known 14 MODY genes. Results The record revealed 1647 studies and among them, 326 studies were accessed for full-text. Finally, 239 studies were included, as per our inclusion criteria. A total of 1017 variants were identified through literature review and 74 unpublished variants from Clinvar database. The gene most commonly affected was GCK, followed by HNF1a. The traditional Sanger sequencing was used in 76 % of the cases and 65 % of the studies were conducted in last 10 years. Variants from countries like Jordan, Oman and Tunisia reported that the MODY types prevalent worldwide were not common in their countries. Conclusions We expect that this paper will help clinicians interpret MODY genetics results with greater confidence. Discrepancies in certain middle-eastern countries need to be investigated as other genes or factors, like consanguinity may be involved in developing diabetes.

show abstract

“…Additionally, HNF4A-MODY can have mild and atypical clinical presentation, again hampering correct diagnosis [ 129 ]. There are also individual features of HNF4A-MODY.…”

Section: Diagnosis and Current Treatment Optionsmentioning

confidence: 99%

Maturity Onset Diabetes of the Young—New Approaches for Disease Modelling

Skoczek

Dulak

Kachamakova‐Trojanowska

2021

IJMS

View full text Add to dashboard Cite

Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous group of monogenic endocrine disorders that is characterised by autosomal dominant inheritance and pancreatic β-cell dysfunction. These patients are commonly misdiagnosed with type 1 or type 2 diabetes, as the clinical symptoms largely overlap. Even though several biomarkers have been tested none of which could be used as single clinical discriminator. The correct diagnosis for individuals with MODY is of utmost importance, as the applied treatment depends on the gene mutation or is subtype-specific. Moreover, in patients with HNF1A-MODY, additional clinical monitoring can be included due to the high incidence of vascular complications observed in these patients. Finally, stratification of MODY patients will enable better and newer treatment options for MODY patients, once the disease pathology for each patient group is better understood. In the current review the clinical characteristics and the known disease-related abnormalities of the most common MODY subtypes are discussed, together with the up-to-date applied diagnostic criteria and treatment options. Additionally, the usage of pluripotent stem cells together with CRISPR/Cas9 gene editing for disease modelling with the possibility to reveal new pathophysiological mechanisms in MODY is discussed.

show abstract

An Atypical HNF4A Mutation Which Does Not Conform to the Classic Presentation of HNF4A-MODY

Cited by 6 publications

References 8 publications

NGS Analysis Revealed Digenic Heterozygous GCK and HNF1A Variants in a Child with Mild Hyperglycemia: A Case Report

NGS Analysis Revealed Digenic Heterozygous GCK and HNF1A Variants in a Child with Mild Hyperglycemia: A Case Report

Causal variants in Maturity Onset Diabetes of the Young (MODY) – A systematic review

Maturity Onset Diabetes of the Young—New Approaches for Disease Modelling

Contact Info

Product

Resources

About