ANALYSIS OF 21 STARGARDTS-DISEASE FAMILIES CONFIRMS A MAJOR LOCUS ON CHROMOSOME 1P WITH EVIDENCE FOR NON-ALLELIC HETEROGENEITY IN A MINORITY OF CASES

Background - Autosomal recessive Stargardt's disease is a macular dege neration characterised by a juvenile onset and a rapidly progressive c ourse resulting in an atrophic macular area typically surrounded by ye llowish retinal flecks. Method - The disease locus has previously been assigned to markers from chromosome 1p21-p13 by genetic linkage analy sis in eight multiplex Stargardt's disease families. Results - In an e xtended analysis, the assignment to chromosome Ip was confirmed in the majority of the 21 families with Stargardt's disease who were studied . In addition, a series of recombinant chromosomes further narrowed th e Stargardt's disease region to an approximately 3 cM interval between markers at D1S424 and D1S497. Conclusion - Multipoint linkage analysi s most probably excludes this locus in three of these families suggest ing non-allelic heterogeneity with at least one additional minor Starg ardt's disease locus.