An Autosomal Dominant Bull’s-Eye Macular Dystrophy (MCDR2) That Maps to Chromosome 4p

Abstract

Abstract: : Purpose: To describe the phenotype of an autosomal dominant macular dystrophy and identify the chromosomal locus. Methods: Eleven members of a three-generation, non-consanguineous British family were examined clinically and also underwent automated perimetry, electrodiagnostic testing, fundus fluorescein angiography and fundus autofluorescence imaging. Blood samples were taken for DNA extraction and linkage analysis was performed. Results: The phenotype is characterised by a ‘bull’s-eye’ macular dystrophy first evident in the first or second decade of life. There is mild visual impairment, central scotomata and electrophysiological testing indicates that most affected individuals have disease confined to the central retina but in older subjects the flash ERG demonstrates more widespread rod and cone abnormalities. Genetic linkage analysis established linkage to chromosome 4p15.2-p16.3 with a maximum LOD score of 3.03 at a recombination fraction of 0.00 for marker D4S391. The locus for this autosomal dominant macular dystrophy lies between flanking markers D4S3023 and D4S3022, and overlaps the Stargardt 4 locus. This region contains the candidate gene PROML1, encoding human prominin (mouse)-like 1 which belongs to the prominin family of five-transmembrane domain proteins. Mutation screening of PROML1 is currently in progress. Conclusions: We report a new locus for Bull’s-eye macular dystrophy on chromosome 4p.

Keywords: macula/fovea • linkage analysis • retina