title: Hyperinsulinaemic hypoglycaemia associated with a heterozygous missense mutation of R1174W in the insulin receptor (IR) gene.
abstract: BACKGROUND
  Mutations in the insulin receptor (IR) gene are known to cause severe insulin resistance. Although clinical features due to a mutation can be diverse, hypoglycaemia is found in some cases. A family with a female proband diagnosed with type A insulin resistance syndrome was studied. Clinical characteristics were compared with the Arginine1174Glutamine (R1174N) mutation reported in the literature.
  
  
  METHODS
  The proband was a 16-year-old girl who was presented with intermittent hypoglycaemia, hirsutism, darkened skin, acne and oligomenorrhoea. A 5-h oral glucose tolerance test (OGTT), intravenous glucose tolerance test and continuous glucose monitoring system were performed for evaluation of glucose metabolism and insulin secretion. Results from a hyperinsulinaemic euglycaemic clamp on the proband were compared to nine normal glucose tolerance (NGT) controls. The IR gene of the proband, along with her parents and two dizygotic twin brothers were scanned for mutations by direct sequencing.
  
  
  RESULTS
  Elevated serum insulin and insulin : C-peptide ratios were found in the proband, the father and one of the twin brothers, carried a heterozygous missense mutation of Arginine1174Tryptophan (R1174W) in exon20 of the IR gene. The clamp study showed that the nonoxidative glucose disposal rates of the proband were near zero, and that the metabolic clearance rate for insulin was markedly reduced.
  
  
  CONCLUSIONS
  R1174 of the IR gene may be a candidate locus for hyperinsulinaemic hypoglycaemia. Clinical heterogeneity is not uncommon within families as well as among mutation carriers with different amino acid replacements. More pedigrees and long-term follow-up data are needed to document the evolution of beta-cell function and clarify the role of R1174 on insulin resistance and hyperinsulinaemic hypoglycaemia.
authors.affiliation: Department of Endocrinology and Diabetes Centre, The First Affiliated Hospital of Sun Yat-sen University, #58 Zhongshan Er Road, Guangzhou, Guangdong, P.R. China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Huang
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Li
authors.forename: Tianyi
authors.initials: T
authors.lastname: Tang
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liao
authors.forename: Bin
authors.initials: B
authors.lastname: Yao
authors.forename: Guoliang
authors.initials: G
authors.lastname: Hu
authors.forename: Jianping
authors.initials: J
authors.lastname: Weng
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics* / Q000473:pathology*; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D011972:Receptor, Insulin / Q000235:genetics*
chemical_list: D011972:Receptor, Insulin