single gene defects causing NIDDM

Last reviewed 02/2023

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.