Fundus Albipunctatus
A number sign (#) is used with this entry because an autosomal dominant form of fundus albipunctatus can be caused by mutation in the RDS gene (PRPH2; 179605) and an autosomal recessive form can be caused by mutation in the RDH5 gene (601617). Furthermore, this fundus picture also occurs in Bietti crystalline corneoretinopathy (210370), an autosomal recessive. See also 180380.0012, which describes an association between this disorder and a mutation in the rhodopsin gene segregating with the APOE epsilon-4 allele (107741) (Souied et al., 1996). Mutation in the RLBP1 gene (180090) has been shown to cause fundus albipunctatus and retinitis punctata albescens.
DescriptionThis form of fleck retina disease (see 228980) is characterized by discrete uniform white dots over the entire fundus with greatest density in the midperiphery and no macular involvement. Night blindness occurs. Both autosomal dominant and autosomal recessive inheritance had been suggested (Krill and Folk, 1962; Krill, 1977).
Clinical FeaturesPearce et al. (1984) described retinitis punctata albescens in association with Bardet-Biedl syndrome (see 209900) in an isolated community in northern Canada.
Fishman et al. (2004) described autosomal recessive retinitis punctata albescens in 5 patients from 3 families. The 3 probands had similar clinical findings: a history of poor night vision, the presence of punctate white deposits in the retina, and substantially reduced or absent rod responses on electroretinogram (ERG) testing.
Niwa et al. (2005) investigated the frequency of cone and rod dysfunction in patients with fundus albipunctatus due to RDH5 mutation. Cone electroretinography showed considerable variability in b-wave amplitudes, and 6 (38%) of 16 patients had b-wave amplitudes smaller than that seen in controls, suggesting extensive cone dysfunction. Cone dysfunction was more severe in older patients. In patients with reduced standard cone ERGs, cone a-wave analysis showed significantly smaller maximal response amplitudes, and rod ERGs were also reduced. Niwa et al. (2005) concluded that reduced full-field cone ERGs were mainly due to loss of cone photoreceptors and the rod system was also affected.
Molecular GeneticsYamamoto et al. (1999) and Gonzalez-Fernandez et al. (1999) identified mutations in the RDH5 gene in patients with fundus albipunctatus (see 601617.0001-601617.0004).
Nakamura and Miyake (2002) reported fundus albipunctatus and a novel macular dystrophy in a 9-year-old boy who was a compound heterozygote for mutations in the RDH5 gene (601617.0006-601617.0007). The authors described the patient's macular findings, visual acuity, and electrophysiologic responses. They concluded that the macular dystrophy was caused by the RDH5 mutations as a phenotype variation of fundus albipunctatus.
Fishman et al. (2004) evaluated the molecular genetic defects associated with autosomal recessive retinitis punctata albescens in 5 patients from 3 families. One of the probands was compound heterozygous for mutations in the RLBP1 gene; her parents manifested round white deposits in the retina. The other 2 probands had no detected pathogenic mutations in the RLBP1 gene or in 3 other genes evaluated: RDH5, RBP3 (180290), and RDH8 (608575).
In a proband with fundus albipunctatus, Cideciyan et al. (2000) found a novel arg157-to-trp (R157W) mutation in the RDH5 gene (601617.0008). Three-dimensional structure modeling and in vitro experiments suggested that this mutation destabilized proper folding and would inactivate the enzyme. Studies using RPE membranes indicated the existence of an alternative oxidizing system for the production of 11-cis-retinal in fundus albipunctatus. The authors concluded that pathways in addition to 11-cis-RDH likely provide 11-cis-retinal to rods and cones and can maintain normal kinetics of visual recovery, but only under certain constraints and less efficiently for cone than for rod function.