posted on 2021-11-17, 16:35authored byKevin Colclough, Sian Ellard, Andrew Hattersley, Kashyap Patel
At present, outside of
infancy, genetic testing for monogenic diabetes is typically for mutations in MODY
genes that predominantly result in isolated diabetes. Monogenic diabetes syndromes
are usually only tested when this is supported by specific syndromic clinical
features. It is not known how frequently patients with suspected MODY have a
mutation in a monogenic syndromic diabetes gene and thus missed by present
testing regimes.
We performedgenetic testing of 27 monogenic diabetes genes (including 18 associated
with syndromic diabetes) for 1280 patients with a clinical suspicion of MODY
from routine clinical care that were not suspected of having monogenic syndromic
diabetes. We confirmed monogenic diabetes in 297 (23%) patients. Mutations in 7
different syndromic diabetes genes accounted for 19% (95%CI 15-24%) of all monogenic diabetes. The
mitochondrial m.3243A>G and mutations in HNF1B were responsible for
the majority of mutations in syndromic diabetes genes. They were also the 4th
and 5th most common causes of monogenic diabetes overall. These patients lacked typical features and their
diabetes phenotypes overlapped with non-syndromic monogenic diabetes patients. Syndromic
monogenic diabetes genes (particularly m.3243A>G and HNF1B) should be routinely tested in patients with suspected MODY that
do not have typical features of a genetic syndrome.
Funding
K.A.P. has a fellowship funded by the Wellcome Trust (219606/Z/19/Z) A.T.H. is a National Institute for Health Research (NIHR) senior investigator. ATH is supported by Wellcome Trust Senior Investigator award (WT098395/Z/12/Z]).