title: A novel point mutation in the insulin gene giving rise to hyperproinsulinemia.
abstract: A 58-yr-old obese white Caucasian male type 2 diabetic, entered into the UK Prospective Diabetes Study, was found to have raised fasting total proinsulin levels 708 pmol/L(-1) (normal range, 3-16 pmol/L(-1)) and normal specific plasma insulin level 29 pmol/L(-1) (normal range, 21-75 pmol/L(-1)). Immunoreactive plasma insulin, measured by RIA, was 503 pmol/L(-1). DNA was extracted, the insulin gene amplified by the PCR, and by direct sequencing, a novel point mutation, G1552C, was identified, which resulted in the substitution of proline (CCT) for arginine (CGT) at position 65. This prevented cleavage of the C-peptide A-chain dibasic cleavage site (lys-arg) by the processing protease in the pancreatic beta-cells. The plasma proinsulin and insulin levels were in accord with expression of both the wild-type and the mutant alleles. The G1552C mutation was not linked with diabetes, because it was present in a 37-yr-old nondiabetic daughter and not in a 35-yr-old daughter who had had gestational diabetes.
authors.affiliation: Diabetes Research Laboratories, Radcliffe Infirmary, Oxford, England.
authors.forename: M G
authors.initials: MG
authors.lastname: Warren-Perry
authors.forename: S E
authors.initials: SE
authors.lastname: Manley
authors.forename: D
authors.initials: D
authors.lastname: Ostrega
authors.forename: K
authors.initials: K
authors.lastname: Polonsky
authors.forename: S
authors.initials: S
authors.lastname: Mussett
authors.forename: P
authors.initials: P
authors.lastname: Brown
authors.forename: R C
authors.initials: RC
authors.lastname: Turner
mesh_terms: D001120:Arginine; D002096:C-Peptide / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis / Q000737:chemistry; D005260:Female; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011384:Proinsulin / Q000097:blood*; D011392:Proline; D017422:Sequence Analysis, DNA
chemical_list: D002096:C-Peptide; D007328:Insulin; D004247:DNA; D011384:Proinsulin; D001120:Arginine; D011392:Proline