A patient with type 2 diabetes mellitus associated with mutations in calcium sensing receptor gene and mitochondrial DNA

Biochem Biophys Res Commun. 2000 Nov 30;278(3):808-13. doi: 10.1006/bbrc.2000.3867.


A 44-year-old female with familial hypocalciuric hypercalcemia (FHH) due to a homozygous missense mutation (Pro40Ala) in calcium sensing receptor (CaSR) gene has type 2 diabetes mellitus. The identical heterozygous mutation of CaSR gene was observed in consanguineous parents and all other family members examined except her two sisters. Many subjects with abnormal glucose tolerance were observed in this family, which is compatible with maternal inheritance. Mitochondrial function of complex I (NADH-coenzyme Q reductase) activity in cybrid cells between mitochondrial DNA (mtDNA)-deleted (rho(0)) HeLa cells and mtDNA from the proband was decreased by 35%. The proband has eight substitutions and among these 4833 A/G is a missense substitution in NADH dehydrogenase 2 gene and may probably be a major pathogenic mutation of impaired complex I activity. These results suggest that coexistence of nuclear gene and mtDNA mutations may have caused or modified the development of abnormal glucose tolerance in this family.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Animals
  • Calcium / metabolism
  • DNA, Mitochondrial / genetics*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Homozygote
  • Humans
  • Hypercalcemia / complications
  • Hypercalcemia / genetics
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism
  • Mutation, Missense*
  • Pedigree
  • Rats
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface / analysis
  • Receptors, Cell Surface / genetics*


  • DNA, Mitochondrial
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface
  • extracellular calcium cation-sensing receptor, rat
  • Calcium