Journal Article

Truncating mutations in <i>FOXC2</i> cause multiple lymphedema syndromes

David N. Finegold, Mark A. Kimak, Elizabeth C. Lawrence, Kara L. Levinson, Elizabeth M. Cherniske, Barbara R. Pober, Jean W. Dunlap and Robert E. Ferrell

in Human Molecular Genetics

Volume 10, issue 11, pages 1185-1189
Published in print May 2001 | ISSN: 0964-6906
Published online May 2001 | e-ISSN: 1460-2083 | DOI:
Truncating mutations in FOXC2 cause multiple lymphedema syndromes

Show Summary Details


Hereditary lymphedemas are developmental disorders of the lymphatics resulting in edema of the extremities due to altered lymphatic flow. One such disorder, the lymphedema-distichiasis syndrome, has been reported to be caused by mutations in the forkhead transcription factor, FOXC2. We sequenced the FOXC2 gene in 86 lymphedema families to identify mutations. Eleven families were identified with mutations predicted to disrupt the DNA binding domain and/or C-terminal α-helices essential for transcription activation by FOXC2. Broad phenotypic heterogeneity was observed within these families. The phenotypes observed overlapped four phenotypically defined lymphedema syndromes. FOXC2 appears to be the primary cause of lymphedema-distichiasis syndrome and is also a cause of lymphedema in families displaying phenotypes attributed to other lymphedema syndromes. Our data demonstrates that the phenotypic classification of autosomal dominant lymphedema does not reflect the underlying genetic causation of these disorders.

Journal Article.  3160 words. 

Subjects: Genetics and Genomics

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