ASSESSMENT OF THE INTERPHOTORECEPTOR MATRIX PROTEOGLYCAN-1 (IMPG1) GENE LOCALIZED TO 6Q13-Q15 IN AUTOSOMAL-DOMINANT STARGARDT-LIKE DISEASE (ADSTGD), PROGRESSIVE BIFOCAL CHORIORETINAL ATROPHY (PBCRA), AND NORTH-CAROLINA MACULAR DYSTROPHY (MCDR1)

We have recently characterised the genomic organisation of a novel int erphotoreceptor matrix proteoglycan, IMPG1, and have mapped the gene l ocus to chromosome 6q13-q15 by fluorescence in situ hybridisation. As the interphotoreceptor matrix (IPM) is thought to play a critical role in retinal adhesion and the maintenance of photoreceptor cells, it is conceivable that a defect in one of the IPM components may cause dege nerative lesions in retinal structures and thus may be associated with human retinopathies. By genetic Linkage analysis, several retinal dys trophies including one form of autosomal dominant Stargardt-like macul ar dystrophy (STGD3), progressive bifocal chorioretinal atrophy (PBCRA ), and North Carolina macular dystrophy (MCDR1) have previously been l ocalised to a region on proximal 6q that overlaps the IMPG1 locus. We have therefore assessed the entire coding region of IMPG1 by exon ampl ification and subsequent single stranded conformational analysis in pa tients from 6q linked multigeneration families diagnosed with PBCRA an d MCDR1, as well as a single patient from an autosomal dominant STGD p edigree unlinked to either of the two known STGD2 and STGD3 loci on ch romosomes 13q and 6q, respectively. No disease associated mutations we re identified. In addition, using an intragenic polymorphism, IMPG1 wa s excluded by genetic recombination from both the PBCRA and the MCDR1 loci. However, as the autosomal dominant Stargardt-like macular dystro phies are genetically heterogeneous, other forms of this disorder, in particular STGD3 previously linked to 6q, may be caused by mutations i n IMPG1.