Exclusion of the cone-specific alpha-subunit of the transducin gene in Stargardt's disease.

Stargardt's disease is an autosomal recessive infantile macular degeneration of unknown origin whose gene has been recently mapped to chromosome 1p21-p13 by linkage analysis in eight multiplex families. Since the cone-specific alpha-subunit of the transducin gene (GNAT2) has been mapped to chromosome 1p13, we tested GNAT2 as the disease-causing gene in our series. Using a novel intragenic polymorphism, we show here that GNAT2 is most probably located centromeric to the genetic interval encompassing the disease gene (D1S424-D1S236, location score = 3.54). In addition, single-strand conformation polymorphism and sequence analyses of the eight exons of the GNAT2 gene was performed in our probands. No evidence of a deleterious base substitution was observed in any affected individual. Taken together, these results support the exclusion of GNAT2 as the causal disease gene of Stargardt's disease. come. The pathogenesis is unknown and the treatment is limited to ultraviolet ray protection with dark glasses. Stargardt's disease has been recently mapped to chromosome 1p21-p13 in the genetic interval defined by loci D1S424 and D1S236. In addition, our previous study has suggested that Stargardt's disease is genetically homogeneous (Kaplan et al. 1993). With respect to the physical mapping of the proteins specific to the retinal pigmentary epithelium or to cones we noted that the cone-specific alpha-subunit of the transducin gene (GNAT2) has been mapped to chromosome 1p13 (Wilkie et al. 1992). The human GNAT2 is 9967 bp in length and consists of eight exons with seven introns (Morris and Fong 1993). In the present study, we examined this gene as the candidate gene in eighteen unrelated patients affected with Stargardt's disease.