Phenotypic variations in a family with retinal dystrophy as result of different mutations in the ABCR gene.
OBJECTIVE
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 cone-rod 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 pigmentosa-like (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.


CONCLUSIONS
Mutations in the ABCR gene can cause clinical pictures resembling autosomal recessive RP and autosomal recessive CRD.
Klevering
B J
BJ
Department of Ophthalmology, University Hospital Nijmegen, Netherlands.
van Driel
M
M
van de Pol
D J
DJ
Pinckers
A J
AJ
Cremers
F P
FP
Hoyng
C B
CB
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003241:Consanguinity; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009755:Night Blindness / Q000235:genetics / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology; D014792:Visual Acuity / Q000235:genetics; D014794:Visual Fields / Q000235:genetics
D018528:ATP-Binding Cassette Transporters