Table 2

Some different approaches to classifying reversions to normal of inherited mutations

Mechanisms (known and unknown)

  • Intragenic recombination (Bloom syndrome)

  • Mitotic gene conversion (epidermolysis bullosa COL17A1)

  • Second site suppressor mutations (in same gene or different gene)

  • Site specific insertion→deletion or vice versa of repeat

  • Site specific insertion/deletion of single nucleotide in nucleotide run (slippage)

  • Expansion/contraction of repeat

  • Site specific single nucleotide reversion (homozygous or hemizygous originally)

Gross effect on phenotype in vivo (modifies ascertainnment)

  • Milder manifestations

  • Slows/abolishes progression of disease

  • Normal areas in vivo (e.g. skin)

  • Normalization of types of cells in blood (+/−disease amelioration)

  • No effect observed in vivo

Effect on cells/tisssue; histology, cell protein cell function: (with or without out culturing in vitro)

  • Reversion to normal function

  • Reversion to presence of protein without function

  • Tissue involved (modifies ascertainment)

Specific genetic disorders