The common p.R114W HNF4A mutation causes a distinct clinical subtype of monogenic diabetes

Diabetes

Volumn 65, Issue 10, 2016, Pages 3212-3217

  Laver, Thomas W ^a   Colclough, Kevin ^a,b   Shepherd, Maggie ^a   Patel, Kashyap ^a   Houghton, Jayne A L ^a,b   Dusatkova, Petra ^c   Pruhova, Stepanka ^c   Morris, Andrew D ^d   Palmer, Colin N ^d   McCarthy, Mark I ^e,f,g   Ellard, Sian ^a,b   Hattersley, Andrew T ^a   Weedon, Michael N ^a  

^a UNIVERSITY OF EXETER   (United Kingdom)

^b ROYAL DEVON AND EXETER NHS FOUNDATION TRUST   (United Kingdom)

^c UNIVERSITY HOSPITAL MOTOL   (Czech Republic)

^d UNIVERSITY OF DUNDEE   (United Kingdom)

^e UNIVERSITY OF OXFORD   (United Kingdom)

^f UNIVERSITY OF OXFORD   (United Kingdom)

^g NIHR OXFORD BIOMEDICAL RESEARCH CENTRE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

HEPATOCYTE NUCLEAR FACTOR 4ALPHA; INSULIN; ORAL ANTIDIABETIC AGENT; SULFONYLUREA; ANTIDIABETIC AGENT; HEPATOCYTE NUCLEAR FACTOR 4; SULFONYLUREA DERIVATIVE;

ADULT; AGED; ARTICLE; ASCERTAINMENT BIAS; BIRTH WEIGHT; CLINICAL FEATURE; COHORT ANALYSIS; CONTROLLED STUDY; DIABETIC PATIENT; DIET THERAPY; DRUG SENSITIVITY; GENETIC ASSOCIATION; GENETIC RISK; GENETIC VARIABILITY; HETEROZYGOTE; HUMAN; INSULIN TREATMENT; LOSS OF FUNCTION MUTATION; MAJOR CLINICAL STUDY; NON INSULIN DEPENDENT DIABETES MELLITUS; ONSET AGE; PENETRANCE; PHENOTYPE; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; TREATMENT RESPONSE; BIOLOGY; DIABETES MELLITUS, TYPE 2; FEMALE; GENETIC PREDISPOSITION; GENETICS; HAPLOTYPE; MALE; MIDDLE AGED; MUTATION; ODDS RATIO; PHYSIOLOGY;

ADULT; AGED; BIRTH WEIGHT; COMPUTATIONAL BIOLOGY; DIABETES MELLITUS, TYPE 2; FEMALE; GENETIC PREDISPOSITION TO DISEASE; HAPLOTYPES; HEPATOCYTE NUCLEAR FACTOR 4; HUMANS; HYPOGLYCEMIC AGENTS; MALE; MIDDLE AGED; MUTATION; ODDS RATIO; SULFONYLUREA COMPOUNDS;

EID: 84989204356     PISSN: 00121797     EISSN: 1939327X     Source Type: Journal    
DOI: 10.2337/db16-0628     Document Type: Article

References (27)

1. Yamagata K, Furuta H, Oda N, et al. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1). Nature 1996;384:458-460
2. Pearson ER, Boj SF, Steele AM, et al. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med 2007;4:e118
3. Shields BM, Hicks S, Shepherd MH, Colclough K, Hattersley AT, Ellard S. Maturity-onset diabetes of the young (MODY): How many cases are we missing? Diabetologia 2010;53:2504-2508
4. Furuta H, Iwasaki N, Oda N, et al. Organization and partial sequence of the hepatocyte nuclear factor-4 alpha/MODY1 gene and identification of a missense mutation, R127W, in a Japanese family with MODY. Diabetes 1997;46:1652-1657
5. Delvecchio M, Ludovico O, Menzaghi C, et al. Low prevalence of HNF1A mutations after molecular screening of multiple MODY genes in 58 Italian families recruited in the pediatric or adult diabetes clinic from a single Italian hospital. Diabetes Care 2014;37:e258-e260
6. Ludovico O, Carella M, Bisceglia L, et al. Identification and clinical characterization of adult patients with multigenerational diabetes mellitus. PLoS One 2015;10:e0135855
7. Exome Aggregation Consortium, Lek M, Karczewski K, et al. Analysis of protein-coding genetic variation in 60,706 humans. bioRxiv. 30 October 2015 [Epub ahead of print]. DOI: 10.1101/030338
8. Shankar RK, Ellard S, Standiford D, et al. Digenic heterozygous HNF1A and HNF4A mutations in two siblings with childhood-onset diabetes. Pediatr Diabetes 2013;14:535-538
9. Navas MA, Munoz-Elias EJ, Kim J, Shih D, Stoffel M. Functional characterization of the MODY1 gene mutations HNF4(R127W), HNF4(V255M), and HNF4(E276Q). Diabetes 1999;48:1459-1465
10. Yang Q, Yamagata K, Yamamoto K, et al. R127W-HNF-4alpha is a loss of function mutation but not a rare polymorphism and causes Type II diabetes in a Japanese family with MODY1. Diabetologia 2000;43:520-524
11. Lausen J, Thomas H, Lemm I, et al. Naturally occurring mutations in the human HNF4a gene impair the function of the transcription factor to a varying degree. Nucleic Acids Res 2000;28:430-437
12. Yaghootkar H, Stancáková A, Freathy RM, et al. Association analysis of 29,956 individuals confirms that a low-frequency variant at CCND2 halves the risk of type 2 diabetes by enhancing insulin secretion. Diabetes 2015;64:2279-2285
13. Wiltshire S, Hattersley AT, Hitman GA, et al. A genomewide scan for loci predisposing to type 2 diabetes in a U.K.population (the Diabetes UK Warren 2 Repository): Analysis of 573 pedigrees provides independent replication of a susceptibility locus on chromosome 1q. Am J Hum Genet 2001;69:553-569
14. Frayling TM, Walker M, McCarthy MI, et al. Parent-offspring trios: A resource to facilitate the identification of type 2 diabetes genes. Diabetes 1999;48: 2475-2479
15. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007;447:661-678
16. Knight B, Shields BM, Hattersley AT. The Exeter Family Study of Childhood Health (EFSOCH): Study protocol and methodology. Paediatr Perinat Epidemiol 2006;20:172-179
17. Dusatkova P, Pruhova S, Borowiec M, et al. Ancestral mutations may cause a significant proportion of GCK-MODY. Pediatr Diabetes 2012;13:489-498
18. Cole TJ, Freeman JV, Preece MA. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Stat Med 1998;17:407-429
19. Wang K, Li M, Hakonarson H. ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 2010;38: E164
20. Chandra V, Huang P, Potluri N, Wu D, Kim Y, Rastinejad F. Multidomain integration in the structure of the HNF-4a nuclear receptor complex. Nature 2013;495:394-398
21. Hamilton AJ, Bingham C, McDonald TJ, et al. The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in addition to a b cell phenotype. J Med Genet 2014;51:165-169
22. Hegele RA, Cao H, Harris SB, Hanley AJ, Zinman B. The hepatic nuclear factor-1a G319S variant is associated with early-onset type 2 diabetes in Canadian Oji-Cree. J Clin Endocrinol Metab 1999;84:1077-1082
23. Harries LW, Sloman MJ, Sellers EA, Hattersley AT, Ellard S. Diabetes susceptibility in the Canadian Oji-Cree population is moderated by abnormal mRNA processing of HNF1A G319S transcripts. Diabetes 2008;57:1978-1982
24. SIGMA Type 2 Diabetes Consortium, Estrada K, Aukrust I, et al. Association of a low-frequency variant in HNF1A with type 2 diabetes in a Latino population. JAMA 2014;311:2305-2314
25. Jafar-Mohammadi B, Groves CJ, Gjesing AP, et al.; DIAGRAM Consortium. A role for coding functional variants in HNF4A in type 2 diabetes susceptibility. Diabetologia 2011;54:111-119
26. 1000 Genomes Project Consortium, Auton A, Brooks LD, et al. A global reference for human genetic variation. Nature 2015;526:68-74
27. Colclough K, Bellanne-Chantelot C, Saint-Martin C, Flanagan SE, Ellard S. Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha and 4 alpha in maturity-onset diabetes of the young and hyperinsulinemic hypoglycemia. Hum Mutat 2013;34:669-685