Lymphedema-ditichiai yndrome and FOXC2 gene mutation

PURPOE: To decribe the clinical characteritic of a family with autoomal dominant lymphedema-ditichiai yndrome and to report the reult of analyi of the FOXC2 gene DEIGN: Obervational and experimental tudy. METHOD: The etting wa a clinical practice. The tudy population wa 17 member of a family with lymphedema-ditichiai. Obervation procedure were complete ophthalmologic examination and collection of blood ample. DNA wa extracted. Mutation analyi of the coding region of the FOXC2 gene wa performed uing direct equencing of polymerae chain reaction (PCR) product and a retriction enzyme aay. The main outcome meaure wa inheritance of mutation in FOXC2 gene. REULT: Nine patient had ditichiai or lymphedema or both and eight did not. equencing of the coding region of the only tranlated exon of the FOXC2 gene revealed a C to A tranverion at poition 939 reulting in a Tyr313top codon with premature termination of tranlation and a truncated protein product. The mutation wa preent in all nine affected individual and in an aymptomatic 9-year-old boy. CONCLUION: Ditichiai-lymphedema yndrome reult from mutation in FOXC2, a member of the forkhead/winged family of trancription factor. There i intrafamilial variation in the clinical expreion of the mutation.