PT - JOURNAL ARTICLE AU - Yasmin Tatour AU - Iker Sanchez-Navarro AU - Elana Chervinsky AU - Hakon Hakonarson AU - Haithum Gawi AU - Saoud Tahsin-Swafiri AU - Rina Leibu AU - Maria Isabel Lopez-Molina AU - Guillermo Fernandez-Sanz AU - Carmen Ayuso AU - Tamar Ben-Yosef TI - Mutations in <em>SCAPER</em> cause autosomal recessive retinitis pigmentosa with intellectual disability AID - 10.1136/jmedgenet-2017-104632 DP - 2017 Aug 09 TA - Journal of Medical Genetics PG - jmedgenet-2017-104632 4099 - http://jmg.bmj.com/content/early/2017/08/09/jmedgenet-2017-104632.short 4100 - http://jmg.bmj.com/content/early/2017/08/09/jmedgenet-2017-104632.full AB - 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.