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


CONCLUSIONS
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.
Steno Diabetes Centre and Hagedorn Research Institute, Gentofte, Denmark. tweb@hagedorn.dk
Trine W
TW
Boesgaard
Stepanka
S
Pruhova
Ehm A
EA
Andersson
Ondrej
O
Cinek
Barbora
B
Obermannova
Jeannet
J
Lauenborg
Peter
P
Damm
Regine
R
Bergholdt
Flemming
F
Pociot
Charlotta
C
Pisinger
Fabrizio
F
Barbetti
Jan
J
Lebl
Oluf
O
Pedersen
Torben
T
Hansen
D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D016640:Diabetes, Gestational / Q000175:diagnosis / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007328:Insulin / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy; D055815:Young Adult
D007328:Insulin