Evaluation of the gene encoding the α subunit of cone transducin in Leber's congenital amaurosis and other retinal dystrophies

Purpose. Alpha cone transducin (ACT) is an important component in the phototransduction cascade of the retina. No retinal disease has been associated with defects in the ACT gene to date. The genetic defect of Leber's congenital amaurosis (LCA), an autosomal recessive blinding retinal dystrophy of the newborn, is not known. We hypothesize that (LCA) is caused by a defect in the ACT gene which prevents proper functioning of the retina. Methods. we obtained DNA from the blood of 12 families with LCA from around the world, 9 families with cone dystrophy (CD) and 3 families with Bardet-Biedl syndrome. We performed SSCP analysis for the 8 exons of ACT and sequenced the positive results. Base pair changes were confirmed by restriction enzyme analysis. Results. We have found 3 new missense mutations. One mutation, Leu-107-Ile, in exon 4, (creates a MbOl site) was found in two Greek families and in 3% of normals. The second mutation, Met-243-Val, in exon 7, (destroys a NsiI site) is present in one LCA family, one family with CD and in 10% of normal alleles. Finally, we found a Leu-148-Phe mutation in one CD family and 3% of controls. Conclusions. In our families, the mutations did not cosegregate perfectly with the disease phenotype. Defects in cone transducin are not a common cause of Leber's congenital amaurosis or cone dystophies. The findings of new intragenic polymorphisms will help for future linkage analysis involving the cone transducin gene.