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Disease | Inheritance | Molecular mechanism |
|---|---|---|
Monogenic diabetes | Autosomal dominant (primary inheritance pattern) | Activating (GOF) |
Monogenic diabetes | Autosomal recessive (rare) | Partially activating + LOF |
Familial hyperinsulinism | Autosomal recessive (Primary inheritance) | LOF |
Familial hyperinsulinism | Autosomal dominant (less common) | Dominant Negative |
Familial hyperinsulinism (FOCAL) | Paternally inherited LOF variant + loss of maternal allele in pancreatic tissue *a single LOF variant is NOT diagnostic for Focal disease per genereviews, due to potential to miss a maternal variant |
Katie Russell is a Broad expert on ABCC8 - she shared these slides https://docs.google.com/presentation/d/1Lw5xnS3-EUYBMeSBMQ9euHRG45imqOWDTQ6KRSdGiw8/edit#slide=id.p Her summary -
CHI
AR - caused by LOF
Some patients with somatic UPD of the pancreas of carriers can develop focal CHI
AD - dominant negative
Did not curate Semidominant monogenic diabetes (MODY) - definitive (GOF / activating mutations by Monogenic diabetes GCEP.); however, there are recessive cases with 1 partially activating and 1 inactivating mutation. This is aka permanent neonatal diabetes. They note that inactivating LOF variants cause hyperinsulinemic hypoglycemia.
Did not curate pulmonary arterial hypertension - not well established per above
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