HGF and MET Mutations in Primary and Secondary Lymphedema.

[lymphedemapeople]

HGF and MET Mutations in Primary and Secondary Lymphedema.

Lymphat Res Biol. 2008

Finegold DN, Schacht V, Kimak MA, Lawrence EC, Foeldi E, Karlsson JM,
Baty CJ, Ferrell RE.
Department of Human Genetics, University of Pittsburgh, Pittsburgh,
Pennsylvania., Department of Pediatrics, University of Pittsburgh,
Pittsburgh, Pennsylvania., DNF, CJB, and REF contributed equally to
this work.

Abstract Background: Lymphedema is the abnormal accumulation of
protein-rich fluid in the interstitial space. Primary lymphedema is a
rare genetic condition with both autosomal dominant and autosomal
recessive modes of inheritance. Three genes, FLT4 (VEGFR3), FOXC2, and
SOX18 cause varying forms of primary lymphedema. In industrialized
countries, secondary lymphedema is usually associated with cancer
therapy and/or trauma. Recent observations suggested that hepatocyte
growth factor/high affinity hepatocyte growth factor receptor (HGF/
MET) were new candidate lymphedema genes. Methods and Results: The
coding exons and flanking regions of HGF and MET were directly
sequenced in 145 lymphedema probands, 59 unrelated women with
secondary lymphedema following treatment for breast cancer, 21
individual patients with lymphedema and intestinal lymphangiectasia,
and at least 159 unrelated ethnic matched control individuals.
Mutations leading to truncation or missense changes in evolutionarily
conserved residues of HGF and MET were identified. These mutations
were not polymorphic in control individuals. Conclusions:The
identification of HGF/MET mutations in primary lymphedema, lymphedema/
lymphangiectasia, and breast cancer-associated secondary lymphedema
suggests that the HGF/MET pathway is causal or alters susceptibility
for a broad range of lymphedema phenotypes. The HGF/MET pathway
provides a new target for the prevention and/or treatment of
lymphedema.

http://www.liebertonline.com/doi/abs/10.1089/lrb.2008.1024

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Pat O'Connor
Lymphedema People
http://www.lymphedemapeople.com