Mutations inSCAPERcause autosomal recessive retinitis pigmentosa with intellectual disability

Abstract

Deleterious 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.

Delineating the expanding phenotype associated with SCAPER gene mutation

“…Recently, a single individual homozygous for a c.2023‐2A>G SCAPER variant presenting with nonsyndromic RP and no evidence of ID was reported in this journal (Jauregui et al, ). The same c.2023‐2A>G SCAPER gene variant has also been reported previously in association with RP, ADHD, and mild ID (Tatour et al, ) indicating the variability in the presence and severity of the extraocular features associated with the SCAPER syndrome (Table ). However, this may also be accounted for by the difficulties in conclusively defining milder developmental delay in some situations, when more subtle clinical findings may not be identified if not specifically assessed.…”

“…In all individuals for whom we have data, progressive loss of night vision begins in first or second decade of life. Together with studies in mice demonstrating expression of SCAPER in multiple retinal layers, particularly in the retinal pigment epithelium and photoreceptor inner and outer segments, this supports a role for SCAPER in photoreceptor function and/or maintenance (Tatour et al, ).…”

“…In the current study, we describe clinical and genetic findings, including seven novel SCAPER variants, in six individuals of Amish, Caucasian, and South Asian descent. Together with our molecular data, our comprehensive phenotypic assessments enable a more detailed clinical comparison to be drawn between the patient cohort described here (including previously published individual G001284; Patient 3 in this study, (Carss et al, ) with the 17 individuals in whom SCAPER variants were recently defined (Hu et al, ; Jauregui et al, ; Najmabadi et al, ; Tatour et al, ; Wormser et al, ), permitting a more precise definition of the clinical phenotype arising from pathogenic SCAPER variation.…”

“…We subsequently reported a single patient with biallelic loss of function (LOF) SCAPER variants associated with retinal disease (Carss et al, ). Biallelic LOF variants have since been associated with ID with or without retinitis pigmentosa (RP) in seven individuals from five families from Spain, Israel, and Iran (Hu et al, ; Tatour et al, ); in one individual from a Jordanian Arab family, a homozygous SCAPER gene variant was identified as the cause of nonsyndromic RP (Jauregui et al, ). More recently, Wormser et al () described a SCAPER gene variant associated with a Bardet–Biedl syndrome (BBS)‐like presentation comprising of ID, RP, short stature, obesity, and brachydactyly in eight individuals from two consanguineous Bedouin families belonging to the same tribe in southern Israel, alongside preliminary functional studies suggesting a possible role for SCAPER in ciliary dynamics and disassembly.…”

A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC)

“…Since 2012, patients’ DNAs were subjected to NGS, using either T‐NGS and/or WES. Novel IRD genes identified by IIRDC members using this approach include MAK , ARL2BP , CEP250 , CEP78 , IDH3A , SCAPER , ARMC9 , and ARSG (Davidson et al, ; Khateb et al, , ; Namburi et al, ; Özgül et al, ; Pierrache et al, ; Tatour et al, ; van de Weghe et al, ; Table S1). In total, 23% of the families were solved using this approach (41% of solved families).…”