[Insulin receptor Arg1131-->Gln: a novel mutation in the catalytic loop of insulin receptor observed in insulin resistant diabetes].
A novel mutation Arg1131-->Gln in the catalytic loop of insulin receptor (IR) associated with insulin resistant diabetes was detected. A 56-year-old male with hyperinsulinemia (fasting IRI 92 microU/ml) showed moderate impairment in glucose tolerance (HbAlc 7.0%, fructosamine 258 mumol/l, fasting glucose 119 mg/dl, maximum value of blood glucose during 75 g OGTT 220 mg/dl). While insulin binding to erythrocytes IR was normal, the insulin-induced autophosphorylation of the patient's erythrocytes IR in vivo showed marked decrease, suggesting this patient had some defect in the kinase domain (exon 17-21) of IR. PCR-SSCP analysis of kinase domain with a genomic DNA obtained from the patient's leucocytes indicated the presence of some mutations in exon 19. Sequencing analysis in M13 revealed a heterozygous mutation at a position 1131 (CGG-->CAG) substituting Gln for Arg. Four people of patient's family analyzed are revealed to have an identical missense mutation at the same position with the patient.
Kasuga
M
M
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Kishimoto
M
M
Hashiramoto
M
M
Yonezawa
K
K
Kazumi
T
T
Hagino
H
H
Shii
K
K
D004247:DNA / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005192:Family Health; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011972:Receptor, Insulin / Q000235:genetics*
D004247:DNA; D011972:Receptor, Insulin