Further evidence that mutations in INScan be a rare cause of Maturity-Onset Diabetes of the Young (MODY)

BMC Medical Genetics

Research Article

Jeannet Lauenborg¹  Peter Damm²  Barbora Obermannova³  Stepanka Pruhova³  Ondrej Cinek³  Jan Lebl³  Fabrizio Barbetti⁴  Charlotta Pisinger⁵  Flemming Pociot⁶  Ehm A Andersson⁶  Trine W Boesgaard⁶  Regine Bergholdt⁶  Torben Hansen⁷  Oluf Pedersen⁸ 

[1] Center for Pregnant Women with Diabetes, Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Denmark;Center for Pregnant Women with Diabetes, Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Denmark;Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark;Department of Pediatrics, Second Faculty of Medicine, Charles University, Prague, Czech Republic;Endocrinology and Diabetes Unit, Department of Paediatric Medicine, Bambino Gesù Children's Hospital IRCCS, Piazza S. Onofrio 4, Rome, Italy;Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark;Steno Diabetes Centre and Hagedorn Research Institute, Gentofte, Denmark;Steno Diabetes Centre and Hagedorn Research Institute, Gentofte, Denmark;Faculty of Health Sciences, University of Southern Denmark, Denmark;Steno Diabetes Centre and Hagedorn Research Institute, Gentofte, Denmark;Institute of Biomedical Science, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark;

关键词: Gestational Diabetes Mellitus;    Oral Glucose Tolerance Test;    Normal Glucose Tolerance;    Oral Hypoglycaemic Agent;    Insulinogenic Index;   

DOI  :  10.1186/1471-2350-11-42

 received in 2009-08-13, accepted in 2010-03-12,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundInsulin gene (INS) mutations have recently been described as a common cause of permanent neonatal diabetes (PNDM) and a rare cause of diabetes diagnosed in childhood or adulthood.MethodsINS was sequenced in 116 maturity-onset diabetes of the young (MODYX) patients (n = 48 Danish and n = 68 Czech), 83 patients with gestational diabetes mellitus (GDM), 34 type 1 diabetic patients screened negative for glutamic acid decarboxylase (GAD), and 96 glucose tolerant individuals. The control group was randomly selected from the population-based sampled Inter99 study.ResultsOne novel heterozygous mutation c.17G>A, R6H, was identified in the pre-proinsulin gene (INS) in a Danish MODYX family. The proband was diagnosed at 20 years of age with mild diabetes and treated with diet and oral hypoglycaemic agent. Two other family members who carried the INS R6H were diagnosed with diabetes when 51 years old and with GDM when 27 years old, respectively. A fourth mutation carrier had normal glucose tolerance when 20 years old. Two carriers of INS R6H were also examined twice with an oral glucose tolerance test (OGTT) with 5 years interval. They both had a ~30% reduction in beta-cell function measured as insulinogenic index. In a Czech MODYX family a previously described R46Q mutation was found. The proband was diagnosed at 13 years of age and had been treated with insulin since onset of diabetes. Her mother and grandmother were diagnosed at 14 and 35 years of age, respectively, and were treated with oral hypoglycaemic agents and/or insulin.ConclusionMutations in INS can be a rare cause of MODY and we conclude that screening for mutations in INS should be recommended in MODYX patients.

【 授权许可】

CC BY   
© Boesgaard et al; licensee BioMed Central Ltd. 2010