Mosaicism can affect any cells or tissue within a developing embryo or at any point after conception to adulthood, and it can be a diagnostic dilemma to determine just how widespread the mosaic pattern is. For example, the population of cells that carry a mutation in a mosaic pregnancy might be found only in extraembryonic tissue and not in the embryo proper (confined placental mosaicism; see Chapter 17), might be present in some tissues of the embryo but not in the gametes (pure somatic mosaicism), might be restricted to the gamete lineage only and nowhere else (pure germline mosaicism), or might be present in both somatic lineages and the germline—all depending on whether the mutation occurred before or after the separation of the inner cell mass, the germline cells, and the somatic cells during embryogenesis (see Chapter 17). Because there are approximately 30 mitotic divisions in the cells of the germline before meiosis in the female and several hundred in the male (see Chapter 2), there is ample opportunity for mutations to occur in germline cells after the separation from somatic cells, resulting in pure gonadal mosaicism.
Determining whether mosaicism for a mutation is present only in the germline or only in somatic tissues may be difficult because failure to find a mutation in a subset of cells from a readily accessible somatic tissue (e.g., peripheral white blood cells, skin, or buccal cells) does not ensure that the mutation is not present elsewhere in the body, including the germline.
Segmental Mosaicism
A mutation affecting morphogenesis and occurring during embryonic development might be manifested as a segmental or patchy abnormality, depending on the stage at which the mutation occurred and the lineage of the somatic cell in which it originated. For example, neurofibromatosis 1 (NF1) (Case 34) is sometimes segmental, affecting only one part of the body. Segmental NF1 is caused by somatic mosaicism for a mutation that occurred after conception. Although the parents of such a patient would be unaffected and considered not at risk for transmitting the mutant gene, a patient with segmental NF1 could be at risk for having an affected child, whose phenotype would be typical for NF1, that is, not segmental. Whether the patient is at risk for transmitting the defect will depend on whether the mutation occurred before separation of germline cells from the somatic cell line that carries the mutation.
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