Universität zu Köln

Schil, KristofVan, Karlstetter, Marcus, Aslanidis, Alexander, Dannhausen, Katharina, Azam, Maleeha, Qamar, Raheel, Leroy, Bart P., Depasse, Fanny, Langmann, Thomas and De Baere, Elfride ORCID: 0000-0002-5609-6895 (2016). Autosomal recessive retinitis pigmentosa with homozygous rhodopsin mutation E150K and non-coding cis-regulatory variants in CRX-binding regions of SAMD7. Sci Rep, 6. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

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

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schil, KristofVan UNSPECIFIED UNSPECIFIED UNSPECIFIED Karlstetter, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Aslanidis, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Dannhausen, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Azam, Maleeha UNSPECIFIED UNSPECIFIED UNSPECIFIED Qamar, Raheel UNSPECIFIED UNSPECIFIED UNSPECIFIED Leroy, Bart P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Depasse, Fanny UNSPECIFIED UNSPECIFIED UNSPECIFIED Langmann, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED De Baere, Elfride UNSPECIFIED orcid.org/0000-0002-5609-6895 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-284375
DOI:	10.1038/srep21307
Journal or Publication Title:	Sci Rep
Volume:	6
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LEBER CONGENITAL AMAUROSIS; RETINAL DEGENERATION; PAKISTANI FAMILIES; GENE; REVEALS; MODIFIER; GENOME; DYSTROPHIES; EXPRESSION; PRPF31 Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28437