2. Academic Validation
  3. Mutations in SCAPER cause autosomal recessive retinitis pigmentosa with intellectual disability

Mutations in SCAPER cause autosomal recessive retinitis pigmentosa with intellectual disability

  • J Med Genet. 2017 Sep 18;54(10):698-704. doi: 10.1136/jmedgenet-2017-104632.
Yasmin Tatour 1,  Iker Sanchez-Navarro 2 3,  Elana Chervinsky 4,  Hakon Hakonarson 5 6,  Haithum Gawi 7,  Saoud Tahsin-Swafiri 2 3,  Rina Leibu 8,  Maria Isabel Lopez-Molina 9,  Guillermo Fernandez-Sanz 9,  Carmen Ayuso 2 3,  Tamar Ben-Yosef 1
Affiliations

Affiliations

  • 1 Rappaport Faculty of Medicine, Technion, Haifa, Israel.
  • 2 Department of Genetics, Health Research Institute-Fundacion Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.
  • 3 CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Instituto de Salud Carlos III, Madrid, Spain.
  • 4 Genetic Institute, Emek Medical Center, Afula, Israel.
  • 5 The Children's Hospital of Philadelphia, The Center for Applied Genomics, Philadelphia, Pennsylvania, USA.
  • 6 Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 7 Clalit Health Services, Sharon-Shomron District, Israel.
  • 8 Alberto Moscona Department of Ophthalmology, Rambam Health Care Campus, Haifa, Israel.
  • 9 Department of Ophthalmology, Fundacion Jimenez DiazUniversity Hospital (FJD), Madrid, Spain.
PMID: 28794130 DOI: 10.1136/jmedgenet-2017-104632
Abstract

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.

Keywords

SCAPER; intellectual disability; retinitis pigmentosa.

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