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Uncovering the complex mysteries of mosaicism



I read with great interest your News feature “Dual identities”, bringing together intriguing results that are starting to emerge in a relatively unrecognized area of human genetics, chimaerism and mosaicism1. It did not, however, cover single-gene mutations leading to somatic mosaicism, or germline mosaicism. I would like to draw readers' attention to these developments because the clinical significance of these observations is probably more far-reaching than previously thought.

One of the initial lines of evidence implicating germline mosaicism in single-gene disorders was haplotype-analysis-based detection of the transmission of a muscular dystrophy gene by an unaffected male2. Today, we know that a significant number of boys born with Duchenne muscular dystrophy are members of families in which one parent carries the disease-causing mutation only in his or her germ cells, an important issue in genetic counselling. It is increasingly being realized that mosaicism in germ cells can be an important underlying cause of disease in a growing number of genetic disorders3.

With respect to somatic mosaicism, we are now beginning to understand the biological mechanism by which some boys with X-linked dominant diseases such as Rett syndrome4 and incontinentia pigmenti5 survive.

Although it is not clear whether single-gene mutations mainly occur as a postzygotic event or before fertilization at the half-chromatid stage6, the presence of an X-linked dominant disease in a male is an important diagnostic sign of somatic mosaicism.


  1. 1

    Pearson, H. Nature 417, 10–11 (2002).

  2. 2

    Darras, B. T. & Francke, U. Nature 329, 556–558 (1987).

  3. 3

    Zlotogora, J. Hum. Genet. 102, 381–386 (1998).

  4. 4

    Topçu, M. et al. Eur. J. Hum. Genet. 10, 77–81 (2002).

  5. 5

    The International Incontinentia Pigmenti Consortium. Am. J. Hum. Genet. 69, 1210–1217 (2001).

  6. 6

    Gartler, S. M. & Francke, U. Am. J. Hum. Genet. 27, 218–223 (1975).

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