Segregation analyses and a genome-wide linkage search confirm genetic heterogeneity and suggest oligogenic inheritance in some Milroy congenital primary lymphedema families

Am J Med Genet. 2001 Feb 1;98(4):303-12. doi: 10.1002/1096-8628(20010201)98:4<303::aid-ajmg1113>;2-9.


We previously described six families with Milroy congenital lymphedema, only one of which showed possible linkage to a candidate locus on chromosome 5 [Witte et al., 1998]. We have now performed a complex segregation analysis of these families, and performed linkage analyses with the other 387 markers used in our genome-wide search. Our results confirm that Milroy lymphedema is generally inherited as a dominant condition. However, this mode of inheritance, as elucidated from the segregation analyses, did not account for all observed familial correlations. The segregation analysis also suggested that shared environmental or additional genetic factors are important in explaining the observed familial aggregation. The finding of linkage to multiple locations in the largest family studied by multipoint parametric mapping (one of which was confirmed by sib-pair non-parametric mapping), suggests that Milroy congenital lymphedema may be oligogenic in this family.

Publication types

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

MeSH terms

  • Chromosome Mapping
  • Chromosomes, Human, Pair 11 / genetics
  • Chromosomes, Human, Pair 18 / genetics
  • Chromosomes, Human, Pair 3 / genetics
  • Chromosomes, Human, Pair 4 / genetics
  • Family Health
  • Female
  • Genetic Heterogeneity*
  • Genome, Human*
  • Humans
  • Lod Score
  • Lymphedema / congenital
  • Lymphedema / genetics*
  • Male
  • Microsatellite Repeats