Mutation of the FOXC2 Gene in a Family with Hereditary Distichiasis

Abstract

Abstract: : Purpose:To examine the FOXC2 gene in a family with simple hereditary distichiasis. Distichiasis-a second row of eyelashes arising from the Meibomian glands of the eyelids-can be inherited either alone (OMIM 12630) or as part of the lymphedema-distichiasis (LD) syndrome (OMIM 153400). Fang et al (Am J Hum Genet, 67:1382-1387, 2000) recently described mutations in the forkhead transcription factor gene, (FOXC2), in families with LD. Heterozygote FOXC2 knockout mice have been reported to have abnormalities of anterior segment development. Methods:. We examined two members of a three-generation family with simple hereditary distichiasis, but without lymphedema or other features of the LD syndrome. Other affected family members were reported to have simple hereditary distichiasis. The FOXC2 gene was PCR amplified from genomic DNA from affected family members and sequenced. Results:Clinical examination revealed distichiasis of all four lids in affected members, but no anterior segment abnormalities or evidence of glaucoma. A cytosine to adenine transversion was found in affected study participants' DNA at position 1074, which would be predicted to cause premature truncation of the protein at codon 359. Conclusion:This finding is important because: (1) it is a novel nonsense mutation in the FOXC2 gene and (2) it suggests that simple hereditary distichiasis and LD are not separate genetic disorders, but different phenotypic expressions of the same underlying disorder.

Keywords: 410 eyelid • 420 genetics • 480 mutations