CRB1-Related Leber Congenital Amaurosis: Reporting Novel Pathogenic Variants and a Brief Review on Mutations Spectrum
CRB1
Leber congenital amaurosis
Retinal dystrophies
Whole exome sequencing
Journal
Iranian biomedical journal
ISSN: 2008-823X
Titre abrégé: Iran Biomed J
Pays: Iran
ID NLM: 9814853
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
entrez:
20
5
2019
pubmed:
20
5
2019
medline:
18
12
2019
Statut:
ppublish
Résumé
LLeber 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. Whole exome sequencing and targeted gene panel were employed. Then validation in the patient and segregation analysis in affected and unaffected members was performed. 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. Our findings show that emerging the next-generation sequencing-based techniques is very efficient in identifying causative variants in disorders with locus heterogeneity.
Sections du résumé
Background
LLeber 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.
Substances chimiques
CRB1 protein, human
0
Eye Proteins
0
Membrane Proteins
0
Nerve Tissue Proteins
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
362-8Références
Nat Genet. 1999 Oct;23(2):217-21
pubmed: 10508521
Nucleic Acids Res. 2000 Jan 1;28(1):235-42
pubmed: 10592235
Arch Ophthalmol. 2001 Mar;119(3):415-20
pubmed: 11231775
Eur J Paediatr Neurol. 2003;7(1):13-22
pubmed: 12615170
Hum Mol Genet. 2003 May 1;12(9):1073-8
pubmed: 12700176
Hum Mutat. 2003 Jun;21(6):577-81
pubmed: 12754702
Acta Ophthalmol (Copenh). 1963;41:317-20
pubmed: 14047474
Ann Hum Biol. 2004 Mar-Apr;31(2):263-9
pubmed: 15204368
Surv Ophthalmol. 2004 Jul-Aug;49(4):379-98
pubmed: 15231395
Hum Mutat. 2004 Nov;24(5):355-69
pubmed: 15459956
Am J Med Genet A. 2005 Jan 1;132A(1):13-9
pubmed: 15580639
Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3052-9
pubmed: 16123401
Prog Retin Eye Res. 2008 Jul;27(4):391-419
pubmed: 18632300
Invest Ophthalmol Vis Sci. 2009 Mar;50(3):1336-43
pubmed: 18936139
Br J Ophthalmol. 2011 Jun;95(6):811-7
pubmed: 20956273
Hum Mutat. 2012 Feb;33(2):306-15
pubmed: 22065545
Eur J Hum Genet. 2013 Mar;21(3):274-80
pubmed: 22968130
Ophthalmic Genet. 2014 Mar;35(1):57-62
pubmed: 23362850
Orphanet J Rare Dis. 2013 Feb 05;8:20
pubmed: 23379534
Invest Ophthalmol Vis Sci. 2013 Mar 01;54(3):2068-75
pubmed: 23449718
Eur J Hum Genet. 2014 Jan;22(1):99-104
pubmed: 23591405
Invest Ophthalmol Vis Sci. 2013 Jun 26;54(6):4351-7
pubmed: 23661368
J Med Genet. 2013 Oct;50(10):674-88
pubmed: 23847139
Semin Ophthalmol. 2013 Sep-Nov;28(5-6):397-405
pubmed: 24138049
Nat Genet. 2014 Mar;46(3):310-5
pubmed: 24487276
Prog Retin Eye Res. 2014 May;40:35-52
pubmed: 24508727
Nat Methods. 2014 Apr;11(4):361-2
pubmed: 24681721
Ophthalmology. 2014 Sep;121(9):1773-82
pubmed: 24811962
Doc Ophthalmol. 2015 Feb;130(1):49-55
pubmed: 25323024
Bioinformatics. 2015 Mar 1;31(5):761-3
pubmed: 25338716
World J Clin Cases. 2015 Feb 16;3(2):112-24
pubmed: 25685757
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
J Intern Med. 2016 Jan;279(1):3-15
pubmed: 26250718
Genet Med. 2016 Nov;18(11):1090-1096
pubmed: 26938784
Ophthalmic Genet. 2017 Mar-Apr;38(2):190-193
pubmed: 27096895
Graefes Arch Clin Exp Ophthalmol. 2016 Sep;254(9):1833-9
pubmed: 27113771
Sci Rep. 2016 Jun 29;6:28755
pubmed: 27353947
Exp Eye Res. 2016 Aug;149:93-99
pubmed: 27375279
Mol Syndromol. 2016 Oct;7(5):274-281
pubmed: 27867342
PLoS One. 2017 Jan 18;12(1):e0170365
pubmed: 28099516
Ophthalmology. 2017 Jun;124(6):884-895
pubmed: 28341475
Br J Ophthalmol. 2017 Sep;101(9):1147-1154
pubmed: 28689169
Sci Rep. 2017 Aug 17;7(1):8654
pubmed: 28819299
Neuropediatrics. 1996 Aug;27(4):189-93
pubmed: 8892367