Assessment of the interphotoreceptor matrix proteoglycan-1 (IMPG1) gene localised to 6q13-q15 in autosomal dominant Stargardt-like disease (ADSTGD), progressive bifocal chorioretinal atrophy (PBCRA), and North Carolina macular dystrophy (MCDR1)

J Med Genet. 1998 Aug;35(8):641-5. doi: 10.1136/jmg.35.8.641.

Abstract

We have recently characterised the genomic organisation of a novel interphotoreceptor matrix proteoglycan, IMPG1, and have mapped the gene locus 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 degenerative lesions in retinal structures and thus may be associated with human retinopathies. By genetic linkage analysis, several retinal dystrophies including one form of autosomal dominant Stargardt-like macular dystrophy (STGD3), progressive bifocal chorioretinal atrophy (PBCRA), and North Carolina macular dystrophy (MCDR1) have previously been localised to a region on proximal 6q that overlaps the IMPG1 locus. We have therefore assessed the entire coding region of IMPG1 by exon amplification and subsequent single stranded conformational analysis in patients from 6q linked multigeneration families diagnosed with PBCRA and MCDR1, as well as a single patient from an autosomal dominant STGD pedigree unlinked to either of the two known STGD2 and STGD3 loci on chromosomes 13q and 6q, respectively. No disease associated mutations were identified. In addition, using an intragenic polymorphism, IMPG1 was excluded by genetic recombination from both the PBCRA and the MCDR1 loci. However, as the autosomal dominant Stargardt-like macular dystrophies are genetically heterogeneous, other forms of this disorder, in particular STGD3 previously linked to 6q, may be caused by mutations in IMPG1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromosome Mapping
  • Chromosomes, Human, Pair 6*
  • DNA Mutational Analysis
  • Extracellular Matrix Proteins / genetics*
  • Eye Proteins*
  • Female
  • Genes, Dominant
  • Glycoproteins / genetics*
  • Humans
  • Macular Degeneration / genetics*
  • Male
  • Pedigree
  • Proteoglycans*
  • Retinal Degeneration / genetics*

Substances

  • Extracellular Matrix Proteins
  • Eye Proteins
  • Glycoproteins
  • IMPG1 protein, human
  • Proteoglycans