How HI is Inherited
There are various ways genetic defects are transferred from parents to children. These include recessive, dominant and sporadic inheritance patterns. There is also an unusual phenomenon called loss of heterozygosity (LOH) which is described below.
Loss of Heterozygosity (LOH)
- In the normal part of the pancreas, the insulin cells inherited a mutated SUR1 gene from the father and a normal SUR1 gene from the mother. These cells have normal insulin secretion.
- In the focal lesion, the insulin cells have lost the normal maternal chromosome during fetal life and because they have only mutant SUR1 genes, they secrete too much insulin. These abnormal cells were able to grow into a distinct focal lesion because they have also lost growth suppressing genes that function only on the maternal (mother’s) chromosome and have duplicated a growth stimulating gene that functions only on the paternal (father’s) chromosome.
- This explains why focal HI can only occur when the KATP mutation is inherited from the father. The loss of the mother’s chromosome is necessary for the focal lesion to develop, but this event occurs after the fetus begins to develop.
- This event is called “loss of heterozygosity” and is not inherited.
- View a diagram of Loss of Heterozygosity (LOH)
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