CLINICAL AND GENETIC STUDY OF 46 ITALIAN PATIENTS WITH PRIMARY LYMPHEDEMA
- S Michelini
- D Degiorgio
- M Cestari
- D Corda
- M Ricci
- M Cardone
- A Mander
- L Famoso
- E Contini
- R Serrani
- L Pinelli
- S Cecchin
- M Bertelli
Abstract
Primary lymphedema is characterized by altered morphological development of lymphatic vessels causing fluid accumulation in interstitial spaces. In familial forms, it is primarily transmitted as a dominant Mendelian trait with heterozygous mutations in genes involved in lymphangiogenesis. We used PCR and direct sequencing to analyze the region of the fms-related tyrosine kinase4 (FLT4) gene encoding the "tyrosine-kinasedomain" and the single exon of the forkhead box C2 (FOXC2) gene in 46 Italian probands with primary lymphedema, 42 of whom had familial forms. We identified 12 mutations in 12 patients (12/46, 26%), six in the FLT4 gene and six in the FOXC2 gene. Most of the mutations (9/12, 75%) were new, and none were identified in 100 healthy subjects or listed in the NCBI dbSNP. A clear relation emerged between genotype and phenotype because 4/5 (80%) probands with onset at birth showed FLT4 mutations and 4/5 (80%) probands without distichiasis and with FOXC2 mutations had an amino-acid substitution outside the forkhead domain. Besides the allelic heterogeneity shown by unique mutations in each proband, the absence of mutations in almost 75% of familial cases of primary lymphedema also suggests genetic heterogeneity.
Keywords: FOXC2, FLT4 alias VEGFR3, primary lymphedema, distichiasis, forkhead domain, genotype-phenotype relationship
How to Cite:
Michelini, S., Degiorgio, D., Cestari, M., Corda, D., Ricci, M., Cardone, M., Mander, A., Famoso, L., Contini, E., Serrani, R., Pinelli, L., Cecchin, S. & Bertelli, M., (2012) “CLINICAL AND GENETIC STUDY OF 46 ITALIAN PATIENTS WITH PRIMARY LYMPHEDEMA”, Lymphology 45(1), 3-12.
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