gonadal mosaicism

In every autosomal dominant disorder, some patients do not have affected parents. In such patients, the disorder results from a new mutation in the egg or the sperm from which they were derived; as such, their siblings are neither affected nor at increased risk of developing the disease.

In some autosomal dominant disorders, exemplified by osteogenesis imperfecta, phenotypically normal parents have more than one affected child. This clearly violates the laws of mendelian inheritance. Studies indicate that gonadal mosaicism may be responsible for such unusual pedigrees.

Gonadal mosaicism results from a mutation that occurs postzygotically during early (embryonic) development. If the mutation affects only cells destined to form the gonads, the gametes carry the mutation, but the somatic cells of the individual are completely normal. Such an individual is said to exhibit germ line or gonadal mosaicism.

A phenotypically normal parent who has germ line mosaicism can transmit the disease-causing mutation to the offspring through the mutant gamete. Because the progenitor cells of the gametes carry the mutation, there is a definite possibility that more than one child of such a parent would be affected. Obviously the likelihood of such an occurrence depends on the proportion of germ cells carrying the mutation.