Mutations in FOXL2Underlying BPES (Types 1 and 2) in Colombian Families

Abstract

ABSTRACT: We report the genetic characterization ofone family with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) type 1and two families with BPES type 2 from a historically isolated population in north-west Colombia. Linkage and haplotype ana-lyses indicate that BPES in these families is linked to 3q23. Mutation screening ofFOXL2in the family with BPES type 1 revealed anovel 394C!T non sense mutation whichdeletes the forkhead DNA binding domain. The two families with BPES type 2 both carryan in-frame 30 bp duplication that leads t othe elongation of a polyalanine tract. This duplication has been previously reported inEurope, where recurrent mutation has beendemonstrated in unrelated familial and spo-radic BPES cases. The recurrent nature ofthis duplication seems to relate to the sec-ondary structure of this DNA region. Thegenotype–phenotype correlation seen inthe Colombian families is consistent with the recent proposal that BPES type 1 iscaused by truncating mutations leading tohaplo insufficiency, while BPES type 2 is dueto mutations generating elongated protein products.