SCAPER-associated nonsyndromic autosomal recessive retinitis pigmentosa

Abstract

Mutations in the gene SCAPER (S-phase CyclinA Associated Protein residing in the Endoplasmic Reticulum) have recently been identified as causing syndromic autosomal recessive retinitis pigmentosa with the extraocular manifestations of intellectual disability and attention-deficit/hyperactivity disorder. We present the case of an 11-year-old boy that presented to our clinic with the complaint of decreased night vision. Clinical presentation, family history, and diagnostic imaging were congruent with the diagnosis of autosomal recessive retinitis pigmentosa. Genetic testing of the patient and both parents via whole-exome sequencing revealed the homozygous mutation c.2023-2A>G in SCAPER. Unique to our patient's presentation is the absence of intellectual disability and attention-deficit/hyperactivity disorder, suggesting that SCAPER-associated retinitis pigmentosa can also present without systemic manifestations.

Keywords: SCAPER; autosomal recessive; retinitis pigmentosa; syndromic disorder.

Figure 1.. Pedigree segregating the SCAPER variant of the proband presented.

The arrow indicates the proband described in this report. Family history is significant for consanguinity, as the proband’s paternal grandmother and maternal grandfather are first cousins. The asymptomatic younger siblings did not undergo clinical examination or genetic testing.

Figure 2.. Multimodal imaging of the proband at presentation.

(a) Color fundus images of the right and left eye, respectively, showed attenuated vessels, pale optic disc, peripheral retina atrophy, and bone-spicule intraretinal pigment migration. (b) Fundus autofluorescence images of the right (top) and left (bottom) eye demonstrated peripheral atrophy and the presence of a hyperautofluorescent ring on the foveal area. The ring is seen in more detail with the 30-degree images (right column). (c) Spectral-domain optical coherence tomography scan through the fovea revealed peripheral thinning of the retina. The ellipsoid zone was disrupted peripherally and conserved in the foveal area. In addition, the foveal border is enlarged and flattened, with a shallow foveal pit (red arrow).

Figure 3.. Schematic of the SCAPER protein demonstrating the different domains and the location of all known pathogenic variants identified in SCAPER relative to the putative domains.

The canonical splice variant (c.2023-A>G) marked in red was identified in our patient and has also been previously reported in two siblings. This variant is predicted to delete 3 residues (E675-K677) in the coiled-coil domain. The p.E620del and p.R727X variants are also located in this region. The p.V373fs*21, p.I991fs*26, and p.S1219N variants are located in predicted unstructured regions of the protein. No known variants are in the putative zinc-finger/C2H2 and transmembrane domains.