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

Catharine J. Holberg, Robert P. Erickson, Michael J. Bernas, Marlys H. Witte, Kimberly E. Fultz, M. Andrade, Charles L. Witte

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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.

Original languageEnglish (US)
Pages (from-to)303-312
Number of pages10
JournalAmerican journal of medical genetics
Issue number4
StatePublished - Feb 1 2001



  • Genome-wide search
  • Milroy congenital lymphedema
  • Multipoint parametric linkage analyses
  • Segregation analysis
  • Sib-pair linkage analysis

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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