Single gene defects causing NIDDM

The following gene defects have been associated with rare inherited forms of NIDDM:

• insulin:
  • autosomal dominant
  • very rare
  • insulin produced is inactive
  • most insulin mutations do not cause diabetes
    
    
• insulin receptor:
  • autosomal dominant or recessive
  • characterised by severe insulin resistance
    
    
• glucokinase:
  • autosomal dominant
  • impairs insulin secretion
  • causes mild but early onset NIDDM (MODY 2)
    
    
• HNF-1 alpha:
  • hepatocyte nuclear factor 1 alpha gene
  • autosomal dominant
  • rare & progressive early onset NIDDM (MODY 3)
    
    
• HNF-4 alpha:
  • hepatocyte nuclear antigen 4 alpha gene
  • autosomal dominant
  • very rare & progressive early onset NIDDM (MODY 1)
    
    
• mitochondrial leucine tRNA:
  • maternal inheritance
  • mutation at nucleotide 3243
  • impaired insulin secretion
  • account for up to 1% of all NIDDM patients
  • may be associated with deafness, MELAS and CEO

Reference:

• O'Rahilly, S. (1997). Non-insulin dependent diabetes mellitus: the gathering storm. BMJ. 314, 955-9.
• Johns, DR. (1996). The other human genome: mitochondrial DNA and disease. Nature Medicine, 2(10), 1065-8.