Clinical characteristics in two patients with partial lipodystrophy and Type A insulin resistance syndrome due to a novel heterozygous missense mutation in the insulin receptor gene

Diabetes Res Clin Pract. 2019 Jun:152:79-87. doi: 10.1016/j.diabres.2019.04.034. Epub 2019 May 16.

Abstract

Aims: The present report aimed to clarify the clinical characteristics in a girl at the age of 12 and her mother with partial lipodystrophy and Type A insulin resistance syndrome.

Methods: We examined fat distribution in the patients using dual-energy X-ray absorptiometry, magnetic resonance imaging, and computed tomography. We performed genetic analysis to examine the causal gene for lipodystrophy and insulin resistance.

Results: Both patients had partial lipodystrophy and a novel heterozygous missense mutation (Asn1137 → Lys1137) in the insulin receptor gene. Because Asn1137 in the catalytic loop is conserved in all protein kinases, this mutation was thought to impair insulin receptor function. By whole-exome sequencing, we found the proband had neither mutations in candidate genes known to be associated with familial partial lipodystrophy nor novel likely candidate causal genes. Taken together, we thought that fat loss in these two patients might be caused by insulin receptor dysfunction. The proband had amenorrhea due to polycystic ovary syndrome. Her menstruation improved, as fat loss was restored during adolescence. This might be caused by improving insulin resistance due to increased levels of leptin and fat mass.

Conclusions: This case might help to understand the mechanisms insulin receptor dysfunction that cause lipodystrophy.

Keywords: Insulin receptor gene mutation; Partial lipodystrophy; Polycystic ovary syndrome; Type A insulin resistance syndrome.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antigens, CD / genetics*
  • Case-Control Studies
  • Child
  • Female
  • Genetic Testing
  • Heterozygote
  • Humans
  • Insulin Resistance / genetics
  • Lipodystrophy, Familial Partial / complications
  • Lipodystrophy, Familial Partial / genetics*
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / genetics*
  • Middle Aged
  • Mutation, Missense*
  • Nuclear Family
  • Pedigree
  • Phenotype
  • Polycystic Ovary Syndrome / complications
  • Polycystic Ovary Syndrome / genetics
  • Receptor, Insulin / genetics*

Substances

  • Antigens, CD
  • INSR protein, human
  • Receptor, Insulin