Human Genetics

, Volume 108, Issue 2, pp 167–173

Back mutation can produce phenotype reversion in Bloom syndrome somatic cells

  • Nathan Ellis
  • Susan Ciocci
  • James German
Original investigation

DOI: 10.1007/s004390000447

Cite this article as:
Ellis, N., Ciocci, S. & German, J. Hum Genet (2001) 108: 167. doi:10.1007/s004390000447

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.

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

Personalised recommendations