Lymphedema-distichiasis syndrome and FOXC2 gene mutation.

PURPOSE: To describe the clinical characteristics of a family with autosomal dominant lymphedema-distichiasis syndrome and to report the results of analysis of the FOXC2 gene

DESIGN: Observational and experimental study.

METHODS: The setting was a clinical practice. The study population was 17 members of a family with lymphedema-distichiasis. Observation procedures were complete ophthalmologic examinations and collection of blood samples. DNA was extracted. Mutation analysis of the coding region of the FOXC2 gene was performed using direct sequencing of polymerase chain reaction (PCR) product and a restriction enzyme assay. The main outcome measure was inheritance of mutation in FOXC2 gene.

RESULTS: Nine patients had distichiasis or lymphedema or both and eight did not. Sequencing of the coding region of the only translated exon of the FOXC2 gene revealed a C to A transversion at position 939 resulting in a Tyr313Stop codon with premature termination of translation and a truncated protein product. The mutation was present in all nine affected individuals and in an asymptomatic 9-year-old boy.

CONCLUSIONS: Distichiasis-lymphedema syndrome results from mutations in FOXC2, a member of the forkhead/winged family of transcription factors. There is intrafamilial variation in the clinical expression of the mutation.