The ABCR gene in recessive and dominant Stargardt diseases: A genetic pathway in macular degeneration

Stargardt disease (STGD) is a juvenile-onset macular dystrophy and can be i nherited in an autosomal recessive or in an autosomal dominant manner. Gene s involved in dominant STDG have been mapped to human chromosomes 13q (STGD 2) and 6q (STGD3), Here, we identify a new kindred with dominant STGD and d emonstrate genetic linkage to the STGD3 locus. Because of a more severe mac ular degeneration phenotype of one of the patients in this family, the gene responsible for the recessive STGD1, ABCR, was analyzed for sequence varia nts in all family members. One allele of the ABCR gene was shown to carry a stop codon-generating mutation (R152X) in three family members, including the one patient who had inherited also the dominant gene. A grandparent of that patient with the same ABCR mutation developed age-related macular dege neration (AMD), consistent with our earlier observation that some variants in the ABCR gene may increase susceptibility to AMD in the heterozygous sta te. Based on these results, we propose that there is a common genetic pathw ay in macular degeneration that includes genes for both recessive and domin ant STGD. (C) 1999 Academic Press.