USA Surgery Today

A number of more recently described concepts have been termed nontraditional inheritance (40:CYTOSOL), in contrast to the Mendelian inheritance patterns described for single-gene conditions. The first of these is mosaicism. This term refers to different genotypes (either different chromosome constitution or alleles at a specific locus:CYTOSOL) in different cells of a single individual. Two types of mosaicism are important, somatic and germline. Somatic mosaicism refers to a postzygotic event that occurs in a single cell. The daughter cells also have the abnormal genotype, leading to two populations of cells in the individual. Although the individual might be less severely affected by the gene mutation than if all cells were affected by the gene change, the actual observed results of this type of change depend on the type of mutation, the gene in which it occurs, the stage in development that it occurs, and the types of cells involved (41:CYTOSOL).

An example of the range of effects of somatic mosaicism can be seen in NF1. Some people with somatic mosaicism for NF1 have generalized disease, clinically indistinguishable from that of nonmosaic patients (42:CYTOSOL). In contrast, some patients with somatic mosaicism have a segmental presentation of their features. For example, a patient with NF1 features limited to the left upper trunk and forearm was shown to have an NF1 gene deletion in fibroblasts from a cafГ©-au-lait spot, but not from blood lymphocytes or unaffected skin (43:CYTOSOL).

Another important concept is germline mosaicism. This refers to two separate populations of cells with different genotypes in the gonads. This concept can be used to explain how two children with an autosomal dominant condition could be born to normal parents. Using molecular genetic techniques, the occurrence of this phenomenon has been confirmed in multiple genetic conditions. For example, a phenotypically normal father with two offspring with NF1 was shown to have a mutation in the NF1 gene in approximately 10% of his spermatozoa. The remainder of his sperm, as well as his lymphocytes, did not demonstrate the mutation (44:CYTOSOL).