Molecular Analysis of The First Reported Hereditary Lymphedema-Distichiasis Case in Bangladesh

Abstract

BackgroundLymphedema–distichiasis syndrome (LD, OMIM 153400) is a hereditary primary lymphedema with autosomal dominant nature of inheritance and variable expression. LD is characterized by late childhood or pubertal onset of lower limb lymphedema and an aberrant second row of eyelashes (distichiasis) arising from the meibomian glands. Underlying molecular causes include mutations in the FOXC2 gene, which codes for a forkhead transcription factor involved in the development of the lymphatic and vascular system. ResultsIn this study, we report the first case of LD from Bangladesh with classical lymphedema–distichiasis syndrome who carries an eight-base-pair deletion in the FOXC2 -gene. ClinVar accession code for this deletion is RCV000007679.3. Although most other mutations of this gene are unique among different families, literature survey indicates this 8 bp deletion has been reported multiples times in independent studies for families from different geographical regions. ConclusionFOXC2 protein is 501 amino acid long. This deletion of 8 bp (ACGCCGCC) causes frameshift of codons after amino acid number 304. The frameshift creates an altered truncated protein with 154 newly amino acids after codon 304. We assume that these changes in the protein may affect its function contributing to the disease manifestations. Further research may confirm these assumptions.