Strand of DNA

What is Monogenic Diabetes?

The overwhelming majority (about 98%) of those with diabetes have either type 1 or type 2 diabetes. These forms of diabetes are described as polygenic, meaning that many genes all contribute and play a role in the development of diabetes, none of them alone being sufficient. However, in a small number of individuals and families, a single gene abnormality can cause diabetes. This is called monogenic diabetes. The single gene abnormality alone is sufficient to cause the diabetes. 

Monogenic diabetes includes:

  • MODY (Maturity Onset Diabetes of the Young)
  • Neonatal diabetes 
  • Syndromic diabetes 

 

Genes and Mutations:

The human body has about 25,000 individual genes. So far, more than 20 have been linked to monogenic diabetes. An error in any one of these genes can cause a child or adult to develop monogenic diabetes, and it can be passed on in the family. 

A gene is a strand of DNA (deoxyribonucleic acid) – essentially a long “ladder” of nucleotide “letters” that are the code or blueprint for proteins that do all the work in all the cells of the body. Genes contain information to pass traits from parents to their children.  If a genetic error occurs, it causes a change in the protein sequence – that is, some of the “rungs” get out of order. This is known as a mutation.

Scientists do not yet understand exactly why genetic mutations occur. We do know that mutations can be:

  • Spontaneous: occurring during fetal development in a person whose parents do not appear to carry the mutation. Spontaneous mutations can then be passed along in future generations. 
  • Hereditary: mutations that are passed along from parent to child 
Picture of doctor with 2 patients - mother and son

MODY

Maturity-Onset Diabetes of the Young (or MODY) is a term used to encompass a group of monogenic forms of diabetes. It accounts for about 1% of people with diabetes. Often patients are misdiagnosed as Type 1/ Type 2 Diabetes or Pre-diabetes. Distinguishing MODY from other forms of diabetes can be difficult for patients and clinicians. Some common features associated with MODY are: 

  • Diabetes develops before the age of 30 years
  • Diabetes often runs in families from one generation to the next 
  • Diabetes may be treated by diet or tablets and does not always need insulin treatment 

Some of the most common MODY genes are listed below - Click on each link to learn more

Quick Links

Mom holding baby

Neonatal Diabetes

Diabetes diagnosed in babies is quite rare. Diabetes diagnosed within the first 6 months of life is called neonatal diabetes mellitus. Neonatal diabetes may be permanent or temporary

Babies diagnosed with diabetes often have a single gene cause (monogenic). Those diagnosed before 6 months of age have an 80% chance of that being linked to a DNA issue. For those diagnosed from 6 months to 1 year, that percentage decreases to about 5%.

The most common genes associated with neonatal diabetes are listed below - Click on each link to learn more 

Quick Links

Other Rare Gene Mutations

Some less common forms of MODY or genetic causes of diabetes are listed below - Click on each to learn more 

Cystic fibrosis related diabetes is a rare cause of diabetes. Cystic fibrosis is caused by inherited a mutated copy of the CFTR gene from both parents. This gene is important for the transport of salt on the surface of cells. Those with cystic fibrosis can have a range of medical problems including abnormal hormone and gut enzyme production from the pancreas. Many with cystic fibrosis related diabetes will require insulin therapy.

EIF2AK3 related diabetes is caused by inherited a mutated copy of the EIF2AK3 gene from both parents. This gene is important in the normal development of beta cells. This is a form of monogenic neonatal diabetes presents within the first few months of life. Insulin therapy is invariably required.

FOXP3 related diabetes is seen primarily in boys as the gene is on the X chromosome. The cause of diabetes is felt to be autoimmune in nature and most boys with a FOXP3 mutation will have a number of other autoimmune problems. Diabetes typically develops in the first year of life.

Mutations within the GATA6 gene can result in neonatal diabetes. The gene is important in the normal development of the pancreas, gut and heart. GATA6 related diabetes is associated with pancreatic, gastrointestinal and cardiac malformations.

GLIS3 related diabetes is a form of monogenic neonatal diabetes caused by inherited a mutated copy of the GLIS3 gene from both parents. Infants with mutations in this gene typically have hypothyroidism from birth and may have multiple other congenital abnormalities.

This gene is important in the regulation of iron storage. Hemachromatosis may develop in those that inherit a mutated copy of the HFE gene from both parents. Diabetes typical occurs in adulthood and presents in men at an earlier age than women.

IER3IP1 related diabetes is a form of monogenic neonatal diabetes caused by inherited a mutated copy of the IER3IP1 gene from both parents. This gene is important in the normal development of beta cells and nerve tissue. Mutations of this gene are associated with significant neurological complications.

NEUROD1 related diabetes is a form of monogenic neonatal diabetes caused by inherited a mutated copy of the NEUROD1 gene from both parents. This gene is important in the normal development of nerve tissue. Significant neurological complications are seen in infants with this form of diabetes.

NEUROG3 related diabetes is a form of monogenic neonatal diabetes caused by inherited a mutated copy of the NEUROG3 gene from both parents. Infants with mutations in this gene typically have severe diarrhea from birth.

PDX1 is a rare cause of MODY or neonatal diabetes. The gene is important in the normal development of the pancreas and affected individuals may have an absent or underdeveloped pancreas.

PTF1A related diabetes is a form of monogenic neonatal diabetes caused by inherited a mutated copy of the PTF1A gene from both parents. This gene is important in the normal development of the brain and the pancreas. Significant neurological complications are seen in infants with this form of diabetes.

PAX6 related diabetes is a form of monogenic neonatal diabetes caused by inherited a mutated copy of the PAX6 gene from both parents. This gene is important in the normal development of the brain and the eyes. Significant neurological complications are seen in infants with this form of diabetes. Some affected individuals will have the eye and neurological problems without diabetes.