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Human Genetics

, Volume 108, Issue 2, pp 167–173 | Cite as

Back mutation can produce phenotype reversion in Bloom syndrome somatic cells

  • Nathan Ellis
  • Susan Ciocci
  • James German
Original investigation

Abstract.

A unique and constant feature of Bloom syndrome (BS) cells is an excessive rate of sister-chromatid exchange (SCE). However, in approximately 20% of persons with typical BS, mosaicism is observed in which a proportion of lymphocytes (usually a small one) exhibits a low-SCE rate. Persons with such mosaicism predominantly are genetic compounds for mutation at BLM, and the low-SCE lymphocytes are the progeny of a precursor cell in which intragenic recombination between the two sites of BLM mutation had generated a normal allele. Very exceptionally, however, persons with BS who exhibit mosaicism are homozygous for the causative mutation. In two such exceptional homozygous persons studied here, back mutation has been demonstrated: one person constitutionally was homozygous for the mutation 1544insA and the other for the mutation 2702G→A. Revertant (low-SCE) lymphoblastoid cells in each person were heterozygous for their mutations, i.e., a normal allele was now present. The normal alleles must have arisen by back mutation in a precursor cell, in one person by the deletion of an A base and, in the other, the nucleotide substitution of a G base for an A base. Thus, back mutation now becomes, together with intragenic recombination, an important genetic mechanism to consider when explaining examples of a reversion of somatic cells to "normal" in persons with a genetically determined abnormal phenotype.

Keywords

Nucleotide Somatic Cell Precursor Cell Nucleotide Substitution Genetic Mechanism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Nathan Ellis
    • 1
  • Susan Ciocci
    • 1
  • James German
    • 2
  1. 1.Department of Human Genetics, Box no. 124, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
  2. 2.Department of Pediatrics, Cornell University Medical College, New York, NY 10021, USA

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