Truncating mutations in FOXC2 cause multiple lymphedema syndromes

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...

Full description

Saved in:
Bibliographic Details
Published in:Human molecular genetics 2001-05, Vol.10 (11), p.1185-1189
Main Authors: FINEGOLD, David N, KIMAK, Mark A, LAWRENCE, Elizabeth C, LEVINSON, Kara L, CHERNISKE, Elizabeth M, POBER, Barbara R, DUNLAP, Jean W, FERRELL, Robert E
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Base Sequence
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Child
Chromosomes, Human, Pair 16 - genetics
Cleft Palate - genetics
Diseases of the lymphatic vessels
DNA Mutational Analysis
DNA Primers - chemistry
DNA-Binding Proteins - genetics
Female
Forkhead Transcription Factors
Humans
Infant, Newborn
Lymphedema - genetics
Male
Medical sciences
Middle Aged
Molecular Sequence Data
Mutation - genetics
Polymerase Chain Reaction
Polymorphism, Genetic
Syndrome
Transcription Factors - genetics
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 alpha-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.
ISSN:0964-6906
1460-2083
1460-2083
DOI:10.1093/hmg/10.11.1185