Back mutation can produce phenotype reversion in Bloom syndrome somatic cells

Hum Genet. 2001 Feb;108(2):167-73. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bloom Syndrome / genetics*
  • Bloom Syndrome / pathology
  • Heterozygote
  • Homozygote
  • Humans
  • Mutation*
  • Phenotype
  • Sister Chromatid Exchange