Autosomal recessive retinitis pigmentosa with homozygous rhodopsin mutation E150K and non-coding cis-regulatory variants in CRX-binding regions of SAMD7

• DOI: 10.1038/srep21307
• Publication Date: 2016-02-18T12:03:50Z
• Authors: Kristof Van Schil; Marcus Karlstetter; Alexander Aslanidis; Katharina Dannhausen; Maleeha Azam; Raheel Qamar; Bart P. Leroy; Fanny Depasse; Thomas Langmann; Elfride De Baere
• Keywords: Coding region

Abstract The aim of this study was to unravel the molecular pathogenesis an unusual retinitis pigmentosa (RP) phenotype observed in a Turkish consanguineous family. Homozygosity mapping revealed two candidate genes, SAMD7 and RHO . A homozygous mutation c.448G > A, p.E150K found affected siblings, while no coding mutations were identified. Interestingly, four non-coding variants genomic regions relevant for binding retinal transcription factor CRX (CRX-bound regions, CBRs) these siblings. Three are located promoter CBR termed CBR1, fourth is more downstream CBR2. Transcriptional activity assessed by luciferase assays electroporation mouse explants with reporter constructs wild-type variant CBRs. combined CBR2/CBR1 construct showed significantly decreased compared sequence, suggesting cis -regulatory effect on expression. As Samd7 recently identified Crx-regulated transcriptional repressor retina, we hypothesize that might contribute here, characterized unusual, recognizable pigment deposits, differing from classic spicular intraretinal pigmentation other individuals typically associated RP general.