Phenotypic variations in a family with retinal dystrophy as result of diVerent mutations in the ABCR gene

Aims—To describe two phenotypic variations of autosomal recessive retinal dystrophy occurring in a consanguineous family in a pseudodominant pattern, resulting from mutations in the ATP binding cassette transporter (ABCR) gene. Methods—Patients of this family underwent an extensive ophthalmic evaluation, including fundus photography, fluorescein angiography, and electroretinography (ERG). Genetic analysis comprised sequence analysis of the retina specific ABCR gene. Results—Five patients presented with decreased visual acuity in the second decade, central chorioretinal atrophy associated with a central scotoma, and severely decreased photopic and scotopic ERG responses. This clinical picture, which in our opinion resembles a conerod dystrophy (CRD), was associated with compound heterozygosity for IVS30+ 1g →t and IVS40+5g→a mutations in the ABCR gene. The four remaining patients presented with night blindness in the first decade because of a retinitis pigmentosalike (RP-like) dystrophy. In addition to a pale “waxy” optic disc, attenuated retinal vessels and bone spicule deposits, a widespread chorioretinal atrophy was observed. The scotopic ERG was extinguished and the photopic ERG was severely diminished. Genetic analysis revealed a homozygous 5' splice mutation IVS30+1g →t in the ABCR gene. Conclusion—Mutations in the ABCR gene can cause clinical pictures resembling autosomal recessive RP and autosomal recessive CRD. (Br J Ophthalmol 1999;83:914–918) Stargardt’s disease (STGD) presents in the first or second decade of life with a bilateral gradual diminution of vision due to progressive atrophy of the macular retinal pigment epithelium and the choriocapillaris in combination with degeneration of the photoreceptors of the posterior pole. STGD is caused by mutations in the retina specific ATP binding cassette transporter (ABCR) gene, which also has been shown to be involved in age related macular degeneration (AMD), although the latter finding has been disputed. We decribe a single consanguineous family with two diVerent phenotypes: cone-rod-like dystrophy (CRD-like) and a retinitis pigmentosa-like dystrophy (RPlike). These phenotypes co-segregated with DNA markers flanking the ABCR gene and subsequent sequence analysis revealed compound heterozygosity (CRD-like) and homozygosity (RP-like) for ABCR mutations. Patients and methods