The "two hit" mechanism of focal hyperinsulinism

(A) The paternally inherited chromosome 11 carries a recessive mutation in the ABCC8 or KCNJ11 genes (black X). In the normal pancreas, the imprinted region of 11p15 (striped area) contains maternally expressed tumor suppressor genes, H19 and CDKN1C, while the paternal region expresses IGF2, a growth promotor.
(B) In the focal lesion, there is somatic loss of the maternal 11p15 region, with paternal uniparental disomy as compensation.