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

We previously described six families with Milroy congenital lymphedema, onl y 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 marke rs used in our genome-wide search. Our results confirm that Milroy lymphede ma is generally inherited as a dominant condition. However, this mode of in heritance, as elucidated from the segregation analyses, did not account for all observed familial correlations. The segregation analysis also suggeste d that shared environmental or additional genetic factors are important in explaining the observed familial aggregation. The finding of linkage to mul tiple locations in the largest family studied by multipoint parametric mapp ing (one of which was confirmed by sib-pair nonparametric mapping), suggest s that Milroy congenital lymphedema may be oligogenic in this family. (C) 2 001 Wiley-Liss, Inc.