Journal Article

Hereditary Lymphedema: Evidence for Linkage and Genetic Heterogeneity

Robert E. Ferrell, Kara L. Levinson, Judith H. Esman, Mark A. Kimak, Elizabeth C. Lawrence, M. Michael Barmada and David N. Finegold

in Human Molecular Genetics

Volume 7, issue 13, pages 2073-2078
Published in print December 1998 | ISSN: 0964-6906
Published online December 1998 | e-ISSN: 1460-2083 | DOI:
Hereditary Lymphedema: Evidence for Linkage and Genetic Heterogeneity

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Hereditary or primary lymphedema is a developmental disorder of the lymphatic system which leads to a disabling and disfiguring swelling of the extremities. Hereditary lymphedema generally shows an autosomal dominant pattern of inheritance with reduced pene-trance, variable expression and variable age at onset. Three multigeneration families demonstrating the phenotype of hereditary lymphedema segregating as an autosomal dominant trait with incomplete pene-trance were genotyped for 366 autosomal markers. Linkage analysis yielded a two-point LOD score of 6.1 at θ = 0.0 for marker D5S1354and a maximum multipoint LOD score of 8.8 at marker D5S1354 located at chromosome 5q34-q35. Linkage analysis in two additional families using markers from the linked region showed one family consistent for linkage to distal chromosome 5. In the second family, linkage to 5q was excluded for all markers in the region with LOD scores Z< − 2.0. The vascular endothelial growth factor C receptor (FLT4) was mapped to the linked region, and partial sequence analysis identified a G→A transition at nucleotide position 3360 of the FLT4 cDNA, predicting a leucine for proline substitution at residue 1126 of the mature receptor in one nuclear family. This study localizes a gene for primary lymphedema to distal chromosome 5q, identifies a plausible candidate gene in the linked region, and provides evidence for a second, unlinked locus for primary lymphedema.

Journal Article.  3290 words.  Illustrated.

Subjects: Genetics and Genomics

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