Retinitis Pigmentosa 37
A number sign (#) is used with this entry because retinitis pigmentosa-37 (RP37) is caused by heterozygous or homozygous mutation in the NR2E3 gene (604485) on chromosome 15q23.
Mutation in the NR2E3 gene is also the cause of enhanced S-cone syndrome (ESCS; 268100).
For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Clinical FeaturesCoppieters et al. (2007) described a 4-generation Belgian family which segregated autosomal dominant retinitis pigmentosa (adRP) in 25 individuals. The phenotype corresponded to that seen in classic adRP, with progressive degeneration of rods and subsequent involvement of cones, further characterized by progressive intraretinal pigment migration, generally of the spicular type. The phenotype also shared some features with enhanced S-cone syndrome. Patients showed a decline of cone function relatively late, at a time when rod function was already undetectable. In addition, the phenotype was characterized by 3 concentric rings of hyperautofluorescence: around the fovea, along the vascular arcades, and in the far periphery. Notably, the 2 more central rings were located in the same areas as those affected in ESCS. The rather limited intraretinal pigmentation seen in later stages was of the mixed and spicular type. In patients without any pigmentation, nummular areas of hypoautofluorescence around the vascular arcades were reminiscent of the pigment clumps observed in ESCS. Coppieters et al. (2007) also described 2 smaller families, one French and the other Belgian, in which affected members had a similar phenotype.
Bernal et al. (2008) described 5 patients from 2 families segregating autosomal recessive retinitis pigmentosa, who had a pattern of round and irregular clumps of pigment in the midperipheral fundus with little or no evidence of bone spicule formation.
MappingCoppieters et al. (2007) performed a genomewide screen in the larger of the 2 Belgian families with adRP described by them and obtained significant linkage to chromosome 15, with marker D15S131 yielding a lod score of 5.10 at theta = 0. Segregation analysis revealed critical recombination events and defined a candidate region of 7.79 cM on chromosome 15q22-q25.
Molecular GeneticsIn 3 families with a novel recognizable clinical subtype of autosomal dominant retinitis pigmentosa, Coppieters et al. (2007) detected a heterozygous missense mutation in the NR2E3 gene (604485.0006) in affected individuals. Homozygous mutations in the same gene cause ESCS, an autosomal recessive condition in which a gain of function of S cones and maldevelopment and/or degeneration of rods leads to increased sensitivity to blue light, night blindness, and central vision loss. Coppieters et al. (2007) proposed a different pathogenetic mechanism for the distinct dominant and recessive NR2E3-related phenotypes that may be attributed to the dual role of NR2E3 in the regulation of photoreceptor-specific genes.
In 5 affected individuals from 2 families segregating autosomal recessive retinitis pigmentosa, Bernal et al. (2008) identified homozygosity for a splice site mutation and a 5-bp deletion in the NR2E3 gene (604485.0001 and 604485.0007, respectively). The splice site mutation had previously been found by Haider et al. (2000) in patients with ESCS.
Kannabiran et al. (2012) studied 26 families from southern India segregating autosomal recessive RP, 16 of which mapped to known autosomal recessive RP or retinal dystrophy genes. Screening of known RP genes revealed mutations in 3 families, including a complex frameshift mutation in the NR2E3 gene (604485.0008) in 2 sibs.