CDHR1 mutations in retinal dystrophies

We report ophthalmic and genetic findings in patients with autosomal recessive retinitis pigmentosa (RP), cone-rod dystrophy (CRD) or cone dystrophy (CD) harboring potential pathogenic variants in the CDHR1 gene. Detailed ophthalmic examination was performed in seven sporadic and six familial subjec...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2017-08, Vol.7 (1), p.6992-6992, Article 6992
Main Authors: Stingl, Katarina, Mayer, Anja K., Llavona, Pablo, Mulahasanovic, Lejla, Rudolph, Günther, Jacobson, Samuel G., Zrenner, Eberhart, Kohl, Susanne, Wissinger, Bernd, Weisschuh, Nicole
Format: Article
Language:English
Subjects:
13/109
38/91
45/22
45/23
45/61
45/77
45/90
631/208/514/2254
692/699/3161/3165
Autosomal recessive inheritance
Cadherins - genetics
Cone-Rod Dystrophies - genetics
Cone-Rod Dystrophies - pathology
Dystrophy
Gene mapping
Genetic Association Studies
Heredity
High-Throughput Nucleotide Sequencing
Homozygosity
Humanities and Social Sciences
Humans
multidisciplinary
Mutation
Nerve Tissue Proteins - genetics
Retina
Retinal degeneration
Retinitis
Retinitis pigmentosa
Retinitis Pigmentosa - genetics
Retinitis Pigmentosa - pathology
Science
Science (multidisciplinary)
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We report ophthalmic and genetic findings in patients with autosomal recessive retinitis pigmentosa (RP), cone-rod dystrophy (CRD) or cone dystrophy (CD) harboring potential pathogenic variants in the CDHR1 gene. Detailed ophthalmic examination was performed in seven sporadic and six familial subjects. Mutation screening was done using a customized next generation sequencing panel targeting 105 genes implicated in inherited retinal disorders. In one family, homozygosity mapping with subsequent candidate gene analysis was performed. Stringent filtering for rare and potentially disease causing variants following a model of autosomal recessive inheritance led to the identification of eleven different CDHR1 variants in nine index cases. All variants were novel at the time of their identification. In silico analyses confirmed their pathogenic potential. Minigene assays were performed for two non-canonical splice site variants and revealed missplicing for the mutant alleles. Mutations in CDHR1 are a rare cause of retinal dystrophy. Our study further expands the mutational spectrum of this gene and the associated clinical presentation.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-07117-8