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

TY - JOUR

T1 - Further evidence that mutations in INS can be a rare cause of Maturity-Onset Diabetes of the Young (MODY)

AU - Boesgaard, Trine W

AU - Pruhova, Stepanka

AU - Andersson, Ehm A

AU - Cinek, Ondrej

AU - Obermannova, Barbora

AU - Lauenborg, Jeannet

AU - Damm, Peter

AU - Bergholdt, Regine

AU - Pociot, Flemming

AU - Pisinger, Charlotta

AU - Barbetti, Fabrizio

AU - Lebl, Jan

AU - Pedersen, Oluf

AU - Hansen, Torben

PY - 2010/3/12

Y1 - 2010/3/12

N2 - Background: Insulin 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.Methods: INS 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.Results: One 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.Conclusion: Mutations in INS can be a rare cause of MODY and we conclude that screening for mutations in INS should be recommended in MODYX patients.

AB - Background: Insulin 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.Methods: INS 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.Results: One 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.Conclusion: Mutations in INS can be a rare cause of MODY and we conclude that screening for mutations in INS should be recommended in MODYX patients.

KW - Diabetes Mellitus, Type 1

KW - Diabetes Mellitus, Type 2

KW - Diabetes, Gestational

KW - Female

KW - Genetic Variation

KW - Humans

KW - Insulin

KW - Male

KW - Mutation

KW - Pedigree

KW - Phenotype

KW - Pregnancy

KW - Young Adult

U2 - 10.1186/1471-2350-11-42

DO - 10.1186/1471-2350-11-42

M3 - Journal article

C2 - 20226046

SN - 1471-2350

VL - 11

SP - 42

JO - B M C Medical Genetics

JF - B M C Medical Genetics

ER -