Identification of two novel mutations in CDHR1 in consanguineous Spanish families with autosomal recessive retinal dystrophy

Scientific Reports
Konstantinos NikopoulosCarmen Ayuso

Abstract

Inherited retinal dystrophies present extensive phenotypic and genetic heterogeneity, posing a challenge for patients' molecular and clinical diagnoses. In this study, we wanted to clinically characterize and investigate the molecular etiology of an atypical form of autosomal recessive retinal dystrophy in two consanguineous Spanish families. Affected members of the respective families exhibited an array of clinical features including reduced visual acuity, photophobia, defective color vision, reduced or absent ERG responses, macular atrophy and pigmentary deposits in the peripheral retina. Genetic investigation included autozygosity mapping coupled with exome sequencing in the first family, whereas autozygome-guided candidate gene screening was performed by means of Sanger DNA sequencing in the second family. Our approach revealed nucleotide changes in CDHR1; a homozygous missense variant (c.1720C>G, p.P574A) and a homozygous single base transition (c.1485+2T>C) affecting the canonical 5' splice site of intron 13, respectively. Both changes co-segregated with the disease and were absent among cohorts of unrelated control individuals. To date, only five mutations in CDHR1 have been identified, all resulting in premature stop co...Continue Reading

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Citations

Jul 10, 2020·Scientific Reports·Imen HabibiLeila El Matri
Aug 3, 2017·Scientific Reports·Katarina StinglNicole Weisschuh
May 29, 2019·Investigative Ophthalmology & Visual Science·Frederick T CollisonRando Allikmets
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Warlen Pereira PiedadeJakub K Famulski
Jun 5, 2020·Journal of Lipid Research·Elliot H ChoiKrzysztof Palczewski
Feb 10, 2021·Journal of Lipid Research·Elliot H ChoiPalczewski Krzysztof
Feb 10, 2020·The Journal of Molecular Diagnostics : JMD·Ana Rodríguez-MuñozJosé M Millán
Jul 8, 2021·Ophthalmic Genetics·Elena MermeklievaRadka Kaneva

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Methods Mentioned

BETA
exome sequencing
PCR

Software Mentioned

Genome Analysis Toolkit ( GATK )
dCHIP
Human Splicing Finder
Sorting Intolerant from Tolerant ( SIFT )
Polyphen -
Mutation Taster
Novoalign
Polymorphism Phenotyping
NetGene 2 Server
SIFT

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