Characterization of two unusual RS1 gene deletions segregating in Danish retinoschisis families

Over 100 distinct retinoschisis gene (RS1) mutations, of which approximatel y 10% are single exon deletions, have been described to date. In this paper we have characterized in detail two dissimilar RS1 gene deletions which ar e accountable for RS in one-third of Danish patients, First, a 136 kb delet ion, spanning from the 5' region of the RS1 gene to intron 3, was identifie d. Unexpectedly this large deletion abolishes exons of three adjacent genes : serine-threonine phosphatase gene (PPEF-1)/serine-threonine protein phosp hatase gene (PP7), retinoschisis gene (RS1), and serine-threonine kinase ge ne (STK9), We demonstrate that the RS1 and STK9 genes are partly overlappin g and the sequences of the PP7 and PPEF-1 genes are identical. This is the first study which reports of retinoschisis patients who also suffer from de letions in genes adjacent to RS1, The 136 kb deletion is also the first gro ss deletion of the retinoschisis gene deleting three exons, It results from a recombination between two repetitive sequences of the Alu family, one in 5' region of the RS1 gene and the other in RSI intron 3, The second altera tion, the actual Danish RS founder mutation, is a 4.4 kb noncontiguous two- part deletion composed of two deleted 1.5 and 2.9 kb segments, separated by an intact 1.2 kb segment. It extends from the 5' flanking region of the re tinoschisis gene to RS intron 1. RS1 gene deletions of this type have not b een identified previously, Despite these two unique deletions, which either lead to severely defective transcription or total absence of the retinosch isin and PPEF-1 protein, all the patients have a typical retinoschisis phen otype, Hum Mutat 16:307-314, 2000, (C) 2000 Wiley-Liss, Inc.