Background Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy, with a worldwide prevalence of 1 in 4000 persons. While in most cases of RP, the disease is limited to the eye (non-syndromic), over 40 forms of syndromic RP have been described.
Objectives To identify the genetic basis for syndromic RP in three unrelated families from Israel and Spain.
Methods Whole exome sequencing was conducted in one Israeli and two Spanish families segregating autosomal recessive RP with intellectual disability. Complete ophthalmic examination included best-corrected visual acuity, funduscopy, optical coherence tomography, fluorescein angiography, flash visual evoked potentials, and electroretinography. Reverse transcription (RT)-PCR and immunostaining were used to examine the spatial and temporal expression pattern of SCAPER.
Results In all patients, biallelic SCAPER mutations were observed. Clinically, patients with SCAPER mutations show signs of typical RP. In addition, they have mild to moderate intellectual disability and attention-deficit/hyperactivity disorder. SCAPER was found to be ubiquitously expressed in a wide range of human tissues, including retina and brain. Furthermore, RT-PCR analysis revealed that in both mouse eye and brain, Scaper is expressed as early as embryonic day 14. In the mouse retina, SCAPER is located in multiple layers, including the retinal pigment epithelium, photoreceptor outer and inner segments, the inner plexiform layer and the ganglion cell layer.
Conclusions Deleterious SCAPER mutations were identified in four patients from three unrelated families of different ethnic backgrounds, thereby confirming the involvement of this gene in the aetiology of autosomal recessive syndromic RP.
- retinitis pigmentosa
- intellectual disability
Statistics from Altmetric.com
Contributors YT and IS-N contributed equally to this work. CA and TB-Y contributed equally to this work. YT, IS-N, ST-S and HH performed the experiments and analysed data. EC, HG, RL, MIL-M and GF-S collected and interpreted clinical data. CA and TB-Y conceived and designed the experiments and wrote the manuscript.
Funding This study was supported by the following research grants: Foundation Fighting Blindness(BR-GE-0214-0639-TECH) to TB and RL; Israel Ministry of Health (3-11893) to TB; CIBER-ER (06/07/0036), FIS(PI013/00226 and PI16-00425), all from FIS Fondo de InvestigaciónSanitaria-ISCIII (FEDER, Spain) to CA; ONCE (Spanish National Association for Blind People) Fundaluce to C.A; Sara Borrell (CD13-00085) FIS -ISCIII(FEDER, Spain) to I.S.N; and an Institutional Development Fund at the Center for Applied Genomics from The Children’s Hospital of Philadelphia to HH. Samples included in the study were stored in FJD-Biobank, Madrid (RD09/0076/00101)
Competing interests None declared.
Ethics approval IRBs at Rambam Health Care Center and Jimenez Diaz Foundation University Hospital.
Provenance and peer review Not commissioned; externally peer reviewed.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.