Molecular cytogenetic evaluation in a patient with a translocation (3;21) associated with blepharophimosis, ptosis, epicanthus inversus syndrome (BPES)

Blepharophimosis, ptosis, epicanthus inversus syndrome type I (BPES; OMIM 1 10100) is an autosomal dominant disorder affecting craniofacial development and ovarian function. We have identified a patient with BPES who carried a de novo reciprocal translocation [46,XX,t(3;21)(q23;q22.1)]. Fluorescence in situ hybridization analysis at band 3q23 using probes derived from BAC 1 75G20 (Research Genetics), PACs 108L15 and 169C10 (RPCI1), and cosmids AC17 4D4, AC68D3, AC44F5, and AC125C5 (Lawrence Livermore National Laboratory) w as performed. The patient's breakpoint was found to lie within the overlapp ing region of the BAC and PACs but centromeric to all the cosmids, However, a 10.5-kb BamHI-digested fragment, common to the BAC and PAC clones, was s hown to cross the breakpoint. The results have placed our patient's breakpo int proximal to that of the previously reported patient [46,XY,t(3;4) (q23; p15.2)] and within a 10.5 kb interval. This is the second patient in which a breakpoint was refined by molecular cytogenetics. Our findings emphasize the significance of this region for BPES, (C) 2000 Academic Press.