dc.contributor.author | Shankar, RK | |
dc.contributor.author | Ellard, Sian | |
dc.contributor.author | Standiford, D | |
dc.contributor.author | Pihoker, C | |
dc.contributor.author | Gilliam, LK | |
dc.contributor.author | Hattersley, Andrew T. | |
dc.contributor.author | Dolan, LM | |
dc.date.accessioned | 2014-02-18T10:58:05Z | |
dc.date.issued | 2013-11-01 | |
dc.description.abstract | Monogenic diabetes due to mutations in the transcription factor genes hepatocyte nuclear factor 1A (HNF1A) and HNF4A is characterized by islet cell antibody negative, familial diabetes with residual insulin secretion. We report two sisters with childhood onset diabetes who are both heterozygous for the most common mutation in each of two transcription factors, HNF1A, and HNF4A. The proband was diagnosed with diabetes at 7 yr of age and treated with insulin for 4 yr. Her genetic diagnosis resulted in transition to sulfonylureas for one and a half years before insulin therapy was re-initiated due to declining glycemic control. Her sister was diagnosed with diabetes at 14 yr of age, treated initially with insulin but has been well controlled on oral sulfonylurea therapy for over 2 yr. Both sisters inherited the HNF4A gene mutation R127W from their mother and the HNF1A gene mutation P291fsinsC (c.872dup) from their father. The father was diagnosed with diabetes at 45 yr of age. Their brother is heterozygous for the HNF4A R127W mutation. Both the brother and mother have normal glucose tolerance at the ages of 16 and 46 yr, respectively. Digenic inheritance of HNF1A and HNF4A mutations is very rare and has only been reported in two families where conclusive evidence for the pathogenicity of their mutations was lacking. Follow-up studies in this family co-segregating the two most commonly reported HNF1A/HNF4A mutations will be informative for understanding the effect of digenic inheritance upon phenotypic severity and response to sulfonylurea therapy. | en_GB |
dc.description.sponsorship | Centers for Disease Control and Prevention. | en_GB |
dc.description.sponsorship | National Institute of Diabetes and Digestive and Kidney Diseases | en_GB |
dc.description.sponsorship | Kaiser Permanente Southern California. | en_GB |
dc.description.sponsorship | University of Colorado Denver. | en_GB |
dc.description.sponsorship | Kuakini Medical Center. | en_GB |
dc.description.sponsorship | Children's Hospital Medical Center (Cincinnati). | en_GB |
dc.description.sponsorship | University of North Carolina at Chapel Hill | en_GB |
dc.description.sponsorship | University of Washington School of Medicine. | en_GB |
dc.description.sponsorship | Wake Forest University School of Medicine. | en_GB |
dc.description.sponsorship | NIH/NCRR | en_GB |
dc.description.sponsorship | Children's Hospital and Regional Medical Center | en_GB |
dc.description.sponsorship | Colorado Pediatric General Clinical Research Center | en_GB |
dc.description.sponsorship | Barbara Davis Center at the University of Colorado at Denver | en_GB |
dc.description.sponsorship | NIH/NCRR at the University of Cincinnati | en_GB |
dc.description.sponsorship | Juvenile Diabetes Research Foundation | en_GB |
dc.identifier.citation | Pediatric Diabetes, 2013, Vol. 14, Issue 7, pp. 535 - 538 | en_GB |
dc.identifier.doi | 10.1111/pedi.12018 | |
dc.identifier.grantnumber | U48/CCU919219 | en_GB |
dc.identifier.grantnumber | U01 DP000246 | en_GB |
dc.identifier.grantnumber | U18DP002714 | en_GB |
dc.identifier.grantnumber | U48/CCU819241-3 | en_GB |
dc.identifier.grantnumber | U01 DP000247 | en_GB |
dc.identifier.grantnumber | U18DP000247-06A1 | en_GB |
dc.identifier.grantnumber | U58CCU919256, U01 DP000245 | en_GB |
dc.identifier.grantnumber | U48/CCU519239, U01 DP000248, 1U18DP002709 | en_GB |
dc.identifier.grantnumber | U48/CCU419249, U01 DP000254, U18DP002708-01 | en_GB |
dc.identifier.grantnumber | U48/CCU919219, U01 DP000250, 200-2010-35171 | en_GB |
dc.identifier.grantnumber | UL1RR029882 | en_GB |
dc.identifier.grantnumber | M01RR00037 | en_GB |
dc.identifier.grantnumber | M01RR00069 | en_GB |
dc.identifier.grantnumber | DERC NIH P30 DK57516 | en_GB |
dc.identifier.grantnumber | 1UL1RR026314-01 | en_GB |
dc.identifier.grantnumber | 9-2007-1700 | en_GB |
dc.identifier.grantnumber | PA numbers 00097, DP-05-069, DP-10-001, contract number 200-2010-35171 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/14544 | |
dc.language.iso | en | en_GB |
dc.publisher | Wiley-Blackwell | en_GB |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pubmed/23551881 | en_GB |
dc.rights.embargoreason | Publisher policy | en_GB |
dc.title | Digenic heterozygous HNF1A and HNF4A mutations in two siblings with childhood-onset diabetes | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2014-11-01T04:00:10Z | |
dc.identifier.issn | 1399-543X | |
dc.description | This is the peer reviewed version of the article, which has been published in final form at 10.1111/pedi.12018. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving. | en_GB |
dc.identifier.journal | Pediatric Diabetes | en_GB |