title: Familiarity, recessivity and germline mosaicism.
abstract: 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.
authors.affiliation: Genetics Laboratory, Department of Biochemistry, Oxford.
authors.forename: J H
authors.initials: JH
authors.lastname: Edwards
mesh_terms: D003241:Consanguinity; D005808:Genes, Recessive; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D005854:Germ Cells; D006801:Humans; D009030:Mosaicism