Mutation of the FOXC2 gene in familial distichiasis.
OBJECTIVE
To examine the FOXC2 gene in a family with hereditary distichiasis.


BACKGROUND
Distichiasis, ie, a second row of eyelashes arising from the meibomian glands of the eyelids, can be inherited either alone (Online Mendelian Inheritance in Man [OMIM] no. 126300) or, more commonly, as part of the lymphedema-distichiasis (LD) syndrome (OMIM no. 153400). More than 45 families with mutations in the FOXC2 gene and LD have been described. Both lymphedema and distichiasis are highly penetrant. Distichiasis without lymphedema is not commonly seen.


METHODS
We examined three generations of a family (N = nine members) with hereditary distichiasis but without lymphedema or other features of LD syndrome. The FOXC2 gene was polymerase chain reaction--amplified from genomic DNA from all family members and examined for mutations.


RESULTS
Clinical examination showed distichiasis of all four lids in two affected family members across two generations. There were no other consistent ophthalmologic abnormalities in the family. A cytosine-to-adenine transversion was identified in DNA from affected study participants at nucleotide position 1076, which would be predicted to cause truncation of the protein at codon 359. This change was not observed in any of the nine unaffected family members participating.


CONCLUSIONS
This finding suggests that hereditary distichiasis and LD may not be separate genetic disorders but different phenotypic expressions of the same underlying disorder. Ophthalmologists should be aware that LD may present as distichiasis alone and counsel and refer their patients appropriately.
Brooks
Brian P
BP
Department of Ophthalmology, University of Michigan, Ann Arbor, MI, USA.
Dagenais
Susan L
SL
Nelson
Christine C
CC
Glynn
Michael W
MW
Caulder
Mark S
MS
Downs
Catherine A
CA
Glover
Thomas W
TW
D000225:Adenine; D000293:Adolescent; D000328:Adult; D001483:Base Sequence / Q000235:genetics; D003062:Codon / Q000235:genetics; D003596:Cytosine; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005124:Eye Abnormalities / Q000235:genetics* / Q000473:pathology; D005140:Eyelashes / Q000002:abnormalities* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*
D003062:Codon; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C082078:mesenchyme fork head 1 protein; D003596:Cytosine; D000225:Adenine