A YAC CONTIG SPANNING THE BLEPHAROPHIMOSIS-PTOSIS-EPICANTHUS INVERSUSSYNDROME AND PROPIONIC ACIDEMIA LOCI

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an auto somal dominant condition consisting of congenital dysplasia of the eye lids with a reduced horizontal diameter of the palpebral fissures, dro opy eyelids and epicanthus inversus. Two clinical entities have been d escribed: type I and type II. The former is distinguished by female in fertility, whereas the latter presents without other symptoms. Both ty pe I and type II were recently mapped on the long arm of chromosome 3 (3q22-q23), suggesting a common gene may be affected. The centromeric and the telomeric limits of this region are well defined between loci D3S1316 and D3S1615, which reside approximately 5 cM apart. Here, we p resent the construction of a YAC contig spanning the entire BPES locus using 17 polymorphic markers, 2 STS and 28 ESTs. This region of appro ximately 5 Mb was covered by 31 YACs, and was supported by detailed FI SH analysis. In addition, we have precisely mapped the propionyl-CoA c arboxylase beta polypeptide (PCCB), the gene mutated in propionic acid emia, within this contig. Apart from providing a framework for the ide ntification of the BPES gene, this contig will also be useful for the future identification of defects and genes mapped to this region, and for developing template resources for genomic sequencing.