Familiarity, recessivity and germline mosaicism

Ann Hum Genet. 1989 Jan;53(1):33-47. doi: 10.1111/j.1469-1809.1989.tb01120.x.


In man evidence of autosomal recessive disease is usually based on a high sib risk, absence of parent-child transmission and increased consanguinity. Discrimination from what are sometimes termed multifactorial disorders and their associated environmental effects is usually based on the latter having a lower recurrence risk, an increased recurrence risk after a second affected child and no increase in consanguinity. Another cause of familial disorders with recurrence restricted to sibs which has received little attention is germline mosaicism for a mutation expressed as a dominant. If, for example, an embryonic mutation resulted in half the precursors of the germ cells carrying a mutation with dominant expression, then the proportion of haploid nuclei conveying the mutation, which is the recurrence risk, would be a quarter. If severity precluded reproduction the disorder would tend to be classified as a recessive. While germline mosaicism will rarely be expressed with such a high recurrence risk, the estimation of this risk in rare disorders is difficult due to extreme and unpredictable bias in ascertainment.

Publication types

  • Review

MeSH terms

  • Consanguinity
  • Genes, Recessive*
  • Genetic Diseases, Inborn / genetics*
  • Germ Cells*
  • Humans
  • Mosaicism*