Retinitis Pigmentosa 45
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-45 (RP45) is caused by homozygous mutation in the gene encoding the beta-1 subunit of the rod photoreceptor cyclic nucleotide-gated channel (CNGB1; 600724) on chromosome 16q21.
For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Clinical FeaturesBareil et al. (2001) identified a consanguineous French family in which typical and severe retinitis pigmentosa segregated as an autosomal recessive trait in 3 affected individuals. The proband had night blindness since early childhood. Later, she experienced loss in the peripheral visual field. At 30 years of age, the fundus showed typical bone spicule-shaped pigmentary deposits. Visual fields were reduced to 10 degrees in both eyes. Electroretinograms exhibited no rod response, whereas cone responses were severely reduced.
Kondo et al. (2004) identified an individual with autosomal recessive retinitis pigmentosa-45. The patient was a 67-year-old Japanese man who had noticed night blindness at school age. He was diagnosed with retinitis pigmentosa at the age of 30 because of visual field defects. Twenty-five years later, after bilateral cataract surgery, dark-adapted flash electroretinograms were nonrecordable in both eyes. A fundus examination revealed a typical bony spicule pigment lesion and nonremarkable macular changes in the left eye, whereas the degeneration involved the macula in the right eye.
MappingUsing linkage analysis, Bareil et al. (2001) mapped the phenotype in their family to chromosome 16q13-q21, with a multipoint lod score of 3.09 for marker D16S3089.
Molecular GeneticsIn affected individuals from a consanguineous French family with retinitis pigmentosa, Bareil et al. (2001) found homozygosity for a missense mutation in exon 30 of the CNGB1 gene (G993V; 600724.0001). The G993V mutation occurs in one of the 3 invariant glycines in the CNGB1 cyclic nucleotide-binding domain, and was predicted to affect binding of cGMP to CNGB1.
In a screen of 59 patients with autosomal recessive retinitis pigmentosa, Kondo et al. (2004) found 1 individual with a homozygous splice site mutation in the CNGB1 gene (600724.0002). The mutation resulted in frameshift and truncation of the protein, with loss of the last 28 amino acids.
Fu et al. (2013) screened 31 unrelated Chinese families with autosomal recessive RP for mutations in 163 retinal disease genes and identified homozygosity for a missense mutation at a conserved residue in the CNGB1 gene (P530R; 600724.0003) that segregated with disease in 1 family.