Diabetes Genes

Monogenic Autoimmunity

Clustering of diabetes and additional autoimmune disease may be caused by a mutation within a single gene. These monogenic autoimmune syndromes show highly variable phenotypes, but generally have an earlier onset and more severe phenotype than common polygenic autoimmunity. A genetic diagnosis may inform medical management, give insight into prognosis and inform families of recurrence risk.1

We offer testing free of charge on a research basis for 15 known monogenic autoimmune genes (AIRE, CD55, CTLA4, DOCK8, FOXP3, IL2RA, ITCH, JAK1, LRBA, NFKB1, SIRT1, SLC29A3, STAT1, STAT3, STAT5B and TNFAIP3) via targeted next generation sequencing. We welcome samples from any patient diagnosed with diabetes and at least one additional autoimmune disorder before the age of five years, no matter what their age is now. In patients without a mutation, gene discovery studies by whole genome sequencing may be employed in order to find the aetiological cause of their disease.

Please fill in the multiple autoimmunity request form (link below) and send with samples. Details of sample requirements and the postal address can be found on the request form. We would strongly recommend sending blood or DNA from both parents as well as the child, as this will allow us to establish rapidly that a genetic mutation is likely to be the cause of the diabetes and autoimmune disease if it has arisen de novo and not present in either unaffected parent.

1 Monogenic autoimmune diseases of the endocrine system. M B Johnson, A T Hattersley, S E Flanagan. Lancet Diabetes Endocrinol. 2016 Oct;4(10):862-72 doi: 10.1016/S2213-8587(16)30095-X. Epub 2016 Jul 26
Multiple Early-Onset Autoimmunity Request Form