For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
12
views
31
references
 Top references
cited by
3
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      211
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      CRB1-Related Leber Congenital Amaurosis: Reporting Novel Pathogenic Variants and a Brief Review on Mutations Spectrum

      case-report

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background:

          Leber congenital amaurosis (LCA) is a rare inherited retinal disease causing severe visual impairment in infancy. It has been reported that 9-15% of LCA cases have mutations in CRB1 gene. The complex of CRB1 protein with other associated proteins affects the determination of cell polarity, orientation, and morphogenesis of photoreceptors. Here, we report three novel pathogenic variants in CRB1 gene and then briefly review the types, prevalence, and correlation of reported mutations in CRB1 gene.

          Methods:

          Whole exome sequencing and targeted gene panel were employed. Then validation in the patient and segregation analysis in affected and unaffected members was performed.

          Results:

          Our detected novel pathogenic variants (p.Glu703*, c.2128+1G>A and p.Ser758SerfsX33) in CRB1 gene were validated by Sanger sequencing. Segregation analysis confirmed the inheritance pattern of the pathogenic variants.

          Conclusion:

          Our findings show that emerging the next-generation sequencing-based techniques is very efficient in identifying causative variants in disorders with locus heterogeneity.

          Related collections

          Most cited references31

          • Record: found
          • Abstract: found
          • Article: not found

          DANN: a deep learning approach for annotating the pathogenicity of genetic variants.

          Daniel Quang, Yifei Chen, Xiaohui Xie (2015)
          Annotating genetic variants, especially non-coding variants, for the purpose of identifying pathogenic variants remains a challenge. Combined annotation-dependent depletion (CADD) is an algorithm designed to annotate both coding and non-coding variants, and has been shown to outperform other annotation algorithms. CADD trains a linear kernel support vector machine (SVM) to differentiate evolutionarily derived, likely benign, alleles from simulated, likely deleterious, variants. However, SVMs cannot capture non-linear relationships among the features, which can limit performance. To address this issue, we have developed DANN. DANN uses the same feature set and training data as CADD to train a deep neural network (DNN). DNNs can capture non-linear relationships among features and are better suited than SVMs for problems with a large number of samples and features. We exploit Compute Unified Device Architecture-compatible graphics processing units and deep learning techniques such as dropout and momentum training to accelerate the DNN training. DANN achieves about a 19% relative reduction in the error rate and about a 14% relative increase in the area under the curve (AUC) metric over CADD's SVM methodology. All data and source code are available at https://cbcl.ics.uci.edu/public_data/DANN/. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
          Article 0 comments Cited 411 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12).

            I. Heredia-de La Cruz, Annemarie Wagemakers, Sudha Bhattacharya … (1999)
            Retinitis pigmentosa (RP) comprises a clinically and genetically heterogeneous group of diseases that afflicts approximately 1.5 million people worldwide. Affected individuals suffer from a progressive degeneration of the photoreceptors, eventually resulting in severe visual impairment. To isolate candidate genes for chorioretinal diseases, we cloned cDNAs specifically or preferentially expressed in the human retina and the retinal pigment epithelium (RPE) through a novel suppression subtractive hybridization (SSH) method. One of these cDNAs (RET3C11) mapped to chromosome 1q31-q32.1, a region harbouring a gene involved in a severe form of autosomal recessive RP characterized by a typical preservation of the para-arteriolar RPE (RP12; ref. 3). The full-length cDNA encodes an extracellular protein with 19 EGF-like domains, 3 laminin A G-like domains and a C-type lectin domain. This protein is homologous to the Drosophila melanogaster protein crumbs (CRB), and denoted CRB1 (crumbs homologue 1). In ten unrelated RP patients with preserved para-arteriolar RPE, we identified a homozygous AluY insertion disrupting the ORF, five homozygous missense mutations and four compound heterozygous mutations in CRB1. The similarity to CRB suggests a role for CRB1 in cell-cell interaction and possibly in the maintenance of cell polarity in the retina. The distinct RPE abnormalities observed in RP12 patients suggest that CRB1 mutations trigger a novel mechanism of photoreceptor degeneration.
            Article 0 comments Cited 114 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              CRB1 mutations in inherited retinal dystrophies.

              Aurore Germain, Aline Antonio, Wassila Carpentier … (2012)
              Mutations in the CRB1 gene are associated with variable phenotypes of severe retinal dystrophies, ranging from leber congenital amaurosis (LCA) to rod-cone dystrophy, also called retinitis pigmentosa (RP). Moreover, retinal dystrophies resulting from CRB1 mutations may be accompanied by specific fundus features: preservation of the para-arteriolar retinal pigment epithelium (PPRPE) and retinal telangiectasia with exudation (also referred to as Coats-like vasculopathy). In this publication, we report seven novel mutations and classify over 150 reported CRB1 sequence variants that were found in more that 240 patients. The data from previous reports were used to analyze a potential correlation between CRB1 variants and the clinical features of respective patients. This meta-analysis suggests that the differential phenotype of patients with CRB1 mutations is due to additional modifying factors rather than particular mutant allele combination. © 2011 Wiley Periodicals, Inc.
              Article 0 comments Cited 72 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Iran Biomed J
                Journal ID (iso-abbrev): Iran. Biomed. J
                Journal ID (publisher-id): IBJ
                Title: Iranian Biomedical Journal
                Publisher: Pasteur Institute of Iran (Tehran, Iran )
                ISSN (Print): 1028-852X
                ISSN (Electronic): 2008-823X
                Publication date (Print): September 2019
                Volume: 23
                Issue: 5
                Pages: 362-368
                Affiliations
                [1 ]Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;
                [2 ]Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;
                [3 ]Farabi Eye Hospital, Tehran, Iran
                Author notes
                [* ]Corresponding Author: Mohammad Keramatipour, Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Tel. & Fax: (+98-21) 88953005; Email: mohammadkeramatipour@gmail.com
                Article
                DOI: 10.29252/.23.5.362
                PMC ID: 6661128
                PubMed ID: 31103025
                SO-VID: 4add4fe5-99a7-47e3-8fa1-41e8abe8f837
                Copyright © © Iranian Biomedical Journal
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 30 July 2018
                Date revision received : 18 August 2018
                Date accepted : 20 August 2018
                Categories
                Subject: Case Report

                Keywords: crb1,leber congenital amaurosis,retinal dystrophies,whole exome sequencing
                Data availability:
                Keywords: crb1, leber congenital amaurosis, retinal dystrophies, whole exome sequencing

                Comments

                Comment on this article

                scite_

                Similar content211

                See all similar

                Cited by3

                See all cited by

                Most referenced authors1,161

                See all reference authors