Identification of three new mutations of the HNF-1 α gene in Japanese MODY families

Ikema, Tomomi; Shimajiri, Yoshinori; Komiya, Ichiro; Tawata, Masato; Sunakawa, S.; Yogi, Hiroyuki; Shimabukuro, Michio; Takasu, Nobuyuki

doi:10.1007/s00125-002-0972-9

Cited by 10 publications

(1 citation statement)

References 26 publications

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“…Q130X at Q130H (17) and G31X at G31D (18) as well as missense mutations where others have been reported, e.g. T521A at T521I (19). A previously undescribed frameshift variant was also found in the 5 0 UTR promoter region; here, a third insertion of c.158-insGGGTTGG occurred, where only two repetitions of the said sequence are known to exist.…”

Section: Discussionmentioning

confidence: 87%

Genetic and clinical characteristics of patients with HNF1A gene variations from the German–Austrian DPV database

Awa

Thon²,

Raile³

et al. 2011

European Journal of Endocrinology

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Objective: To determine prevalence, genetic and phenotype characteristics of patients with hepatocyte nuclear factor-1a (HNF1A) variants in the Diabetes Patienten Verlaufsdokumenation (DPV) multicentre database and to examine the influence of HNF1A mutation type, or location on clinical phenotypes. Patients and methods: Seventy-one DPV patients were labelled as HNF1A-MODY (MODY3). Forty-four patients carried HNF1A mutations, while 27 patients were found to have HNF1A polymorphisms only. Associations between mutation type/position and age at disease onset, HbAlc, body mass index (BMI), diagnosis, family history and treatment modality were analysed using non-parametric statistics (Wilcoxon test). Results: Patients with HNF1A mutations were 36% male, aged 14.1G5.8 years at diagnosis, and slightly overweight (BMI-SDS: C0.8G1.1). Treatment was lifestyle intervention (20.5%), insulin (35.3%), oral anti-diabetic (OAD, 43%) and both insulinCOAD (15.9%). More patients with missense mutations (60%) than patients with nonsense mutations/frameshift (23.8%) did not use insulin (PZ0.03). No differences were found with regard to mutation types, isoform or domain. We identified several previously undescribed mutations in the cohort including c.-158insGGGTTGG in the promoter region, G31X, E41X, Q130X, L162P, R245I, A269P, S355X, Q398X, Q473X, Q495X, E508X, P588fs-insGCCA and P588fs-delAC. Patients carrying HNF1A polymorphisms were significantly younger at diagnosis than patients with HNF1A mutations (10.9G4.2 vs 14.19G5.8 years; PZ0.027), and all carried I27L, S487N and A98V (nZ3). Conclusion: HNF1A-MODY is the second most frequent MODY diagnosis registered in the DPV database, and previously undescribed HNF1A mutations account for about one-third of HNF1A-MODY cases. Patients with HNF1A polymorphisms documented as HNF1A-MODY were misclassified. They may have autoantibody-negative type 1B or type 2 diabetes or may have other MODY types.

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Section: Discussionmentioning

confidence: 87%

Genetic and clinical characteristics of patients with HNF1A gene variations from the German–Austrian DPV database

Awa

Thon²,

Raile³

et al. 2011

European Journal of Endocrinology

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Current literature in diabetes

2003

Diabetes Metabolism Res

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 17 sections: 1 Books, Reviews & Symposia; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Prediction; 7 Prevention; 8 Intervention: a) General; b) Pharmacology; 9 Pathology: a) General; b) Cardiovascular; c) Neurological; d) Renal; 10 Endocrinology & Metabolism; 11 Nutrition; 12 Animal Studies; 13 Techniques. Within each section, articles are listed in alphabetical order with respect to author (9 Weeks journals ‐ Search completed at 5th February 2003)

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Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in maturity-onset diabetes of the young

2006

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Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset (often <25 years of age), and pancreatic beta-cell dysfunction. MODY is both clinically and genetically heterogeneous, with six different genes identified to date; glucokinase (GCK), hepatocyte nuclear factor-1 alpha (HNF1A, or TCF1), hepatocyte nuclear factor-4 alpha (HNF4A), insulin promoter factor-1 (IPF1 or PDX1), hepatocyte nuclear factor-1 beta (HNF1B or TCF2), and neurogenic differentiation 1 (NEUROD1). Mutations in the HNF1A gene are a common cause of MODY in the majority of populations studied. A total of 193 different mutations have been described in 373 families. The most common mutation is Pro291fs (P291fsinsC) in the polycytosine (poly C) tract of exon 4, which has been reported in 65 families. HNF4A mutations are rarer; 31 mutations reported in 40 families. Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. The identification of an HNF1A or 4A gene mutation confirms a diagnosis of MODY and has important implications for clinical management.

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Identification of three new mutations of the HNF-1 α gene in Japanese MODY families

Cited by 10 publications

References 26 publications

Genetic and clinical characteristics of patients with HNF1A gene variations from the German–Austrian DPV database

Genetic and clinical characteristics of patients with HNF1A gene variations from the German–Austrian DPV database

Current literature in diabetes

Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in maturity-onset diabetes of the young

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