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

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Version: Final published version
Serval ID
serval:BIB_E5B61BAA557D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of two novel mutations in CDHR1 in consanguineous Spanish families with autosomal recessive retinal dystrophy.
Journal
Scientific Reports
Author(s)
Nikopoulos K., Avila-Fernandez A., Corton M., Lopez-Molina M.I., Perez-Carro R., Bontadelli L., Di Gioia S.A., Zurita O., Garcia-Sandoval B., Rivolta C., Ayuso C.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
5
Pages
13902
Language
english
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 codons leading to mRNA nonsense mediated decay. Our work reports two previously unidentified homozygous mutations in CDHR1 further expanding the mutational spectrum of this gene.
Pubmed
Web of science
Open Access
Yes
Create date
29/09/2015 16:23
Last modification date
20/08/2019 16:09
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