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The early onset of multiple drusen in the posterior pole of the retina is characteristic of a group of macular dystrophies often referred to as dominant or radial drusen. At least two forms, Doyne honeycomb retinal dystrophy (DHRD) and Malattia Leventinese (MLVT), are associated with a single missense mutation (R345W) in the gene encoding the EGF-containing fibulin-like extracellular matrix protein-1 (EFEMP1) and are now thought to represent a single entity. Here, we present a further evaluation of the role of EFEMP1 in the pathogenesis of sporadic forms of early onset drusen. We analyzed all coding exons of the EFEMP1 gene by SSCP analysis in 14 unrelated individuals with early onset of multiple drusen and no apparent family history of the disease. In this patient group, we did not detect the R345W mutation or any other disease-associated mutation. Three different polymorphisms and two intragenic polymorphic repeats were present in similar frequencies in the patients and control individuals. We conclude that EFEMP1 is unlikely to be involved in the disease in this patient group. This suggests that mutations in a different as yet unknown gene or genes may lead to the early onset drusen phenotype. [ABSTRACT FROM AUTHOR]

We have cloned and characterized a novel gene (C11orf9) mapping to chromosome 11q12→q13.1. The transcript was initially identified as a partial cDNA sequence in the course of constructing a transcript map of the region between markers D11S1765 and uteroglobin known to encompass the gene causing Best disease. Using a combination of EST mapping, computational exon prediction, RT-PCR, and 5′-RACE its 5.7-kb full-length cDNA sequence was subsequently obtained. The C11orf9 gene consists of 26 exons spanning 33.1 kb of genomic DNA and is located about 4.3 kb centromeric to FEN1. Biocomputational analysis predicts that its conceptualtranslation product of 1,111 amino acids contains two transmembrane helices as well as two proline-rich regions. Alignment reveals significant homology to hypothetical peptides from several other species including C. elegans and D. melanogaster , indicating a high degree of conservation throughout evolution. Northern Blot and RT-PCR analyses demonstrate widespread expression of a single transcript but varying degrees of abundance among the individual tissues tested. Mutation analysis of the entire coding sequence excluded C11orf9 as the Best disease gene. Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The interphotoreceptor matrix is a unique extracellular matrix occupying the space between the photoreceptors and the retinal pigment epithelium. Due to its putative function in the maintenance and integrity of the photoreceptor cells, it is conceivable that it is involved in retinal degeneration processes. More recently, a novel gene encoding a 150-kDa interphotoreceptor matrix proteoglycan, designated IMPG1, was cloned and shown to be expressed in both rod and cone photoreceptor cells. To assess this gene in human retinal dystrophies, we have now determined the genomic organization and chro- mosome location of IMPG1. It is composed of 17 exons ranging from 21 to 533 bp, including an alternatively spliced exon 2. Using somatic cell hybrid mapping and FISH analysis, we have assigned the IMPG1 locus to 6q13→q15. As this interval overlaps with the chromosomal loci of several human retinopathies, including autosomal dominant Stargardt-like macular dystrophy (STGD3), progressive bifocal chorioretinal atrophy (PBCRA), and North Carolina macular dystrophy (MCDR1), IMPG1 represents an attractive candidate for these 6q-linked disorders. [ABSTRACT FROM AUTHOR]