Physical mapping and genomic structure of the Lowe syndrome gene OCRL1.

The oculocerebrorenal syndrome of Lowe (OCRL; McKusick 309,000) is a rare X-linked disorder characterized by mental retardation, congenital cataracts, and Fanconi syndrome of the proximal renal tubules. We have carried out physical mapping of the OCRL1 gene and determined that it contains 24 exons occupying 58 kb. The gene, located in Xq25-26, is transcribed in a centromeric to telomeric direction. Primers have been developed that allow all coding exons and their intron/exon boundaries to be amplified from genomic DNA for mutation detection. Two tetranucleotide tandem repeat polymorphisms were characterized that immediately flank the OCRL1 gene and, together, are informative in over 90% of females. Variable splicing was seen in the OCRL1 transcript, involving a small 24-bp exon. These results should prove useful to medical and molecular geneticists studying mutations and providing DNA diagnostic services to families dealing with Lowe syndrome as well as to cell biologists interested in structure-function relationships for the OCRL1 protein.