Characterization of the human diacylglycerol kinase epsilon gene and its assessment as a candidate for inherited retinitis pigmentosa.

Abstract

Human diacylglycerol kinase epsilon (hDGK epsilon) displays high selectivity for arachidonate-containing substrates and may be essential in the termination of signals transmitted through arachidonoyl-diacylglycerol and/or the synthesis of phospholipids with defined fatty acid composition. We herein report the genomic structure, chromosomal mapping, and mutation screening of hDGK epsilon gene. hDGK epsilon gene contains at least 12 exons spanning approximately 30 kb of genomic sequence and was mapped to chromosome 17q22 by fluorescence in situ hybridization. A search for disease gene linkage revealed that a locus for autosomal dominant retinitis pigmentosa (adRP) known as RP17 resided in that region, and Northern blot analysis showed that hDGK epsilon was expressed in human retina. The hDGK epsilon gene was then localized to one of the YAC clones containing a STS marker for the RP17 locus by YAC contig mapping. Direct sequencing following PCR amplification of two affected DNA samples from that type of adRP patients, however, did not reveal any mutation in hDGK epsilon exons.