scholarly journals Whole-exome sequencing identifies OR2W3 mutation as a cause of autosomal dominant retinitis pigmentosa

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Xiangyu Ma ◽  
Liping Guan ◽  
Wei Wu ◽  
Yao Zhang ◽  
Wei Zheng ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Dominant ◽  
Autosomal Dominant Retinitis Pigmentosa ◽  
Whole Exome

scholarly journals Application of Whole Exome Sequencing in Six Families with an Initial Diagnosis of Autosomal Dominant Retinitis Pigmentosa: Lessons Learned

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0133624 ◽  
Author(s):  
Berta Almoguera ◽  
Jiankang Li ◽  
Patricia Fernandez-San Jose ◽  
Yichuan Liu ◽  
Michael March ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Dominant ◽  
Lessons Learned ◽  
Initial Diagnosis ◽  
Autosomal Dominant Retinitis Pigmentosa ◽  
Whole Exome

scholarly journals A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy

2021 ◽  
Author(s):  
Qing Li ◽  
Chengfeng Wang ◽  
Wei Li ◽  
Zaiqiang Zhang ◽  
Shanshan Wang ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Skin Biopsy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Dominant ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Collagen Type Iv ◽  
Lacunar Infarcts ◽  
Whole Exome

AbstractPontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL) is a rare hereditary cerebral small vessel disease. We report a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL. The index case was followed up for 6 years. Neuroimaging, whole-exome sequencing, skin biopsy, and pedigree analysis were performed. She initially presented with minor head injury at age 38. MRI brain showed chronic lacunar infarcts in the pons, left thalamus, and right centrum semiovale. Extensive workup was unremarkable except for a patent foramen ovale (PFO). Despite anticoagulation, PFO closure, and antiplatelet therapy, the patient had recurrent lacunar infarcts in the pons and deep white matter, as well as subcortical microhemorrhages. Whole-exome sequencing demonstrated a novel c.*34G > T mutation in the 3′ untranslated region of COL4A1 gene. Skin biopsy subsequently demonstrated thickening of vascular basement membrane, proliferation of endothelial cells, and stenosis of vascular lumen. Three additional family members had gene testing and 2 of them were found to have the same heterozygous mutation. Of the 18 individuals in the pedigree of 3 generations, 12 had clinical and MRI evidence of PADMAL. The mechanisms of both ischemic and hemorrhagic stroke are likely the overexpression of COLT4A1 in the basement membrane and frugality of the vessel walls. Our findings suggest that the novel c.*34G > T mutation appears to have the same functional consequences as the previously reported COL4A1 gene mutations in patients with PADMAL and multi-infarct dementia of Swedish type.

scholarly journals Whole-exome sequencing reveals POC5 as a novel gene associated with autosomal recessive retinitis pigmentosa

2017 ◽  
Vol 27 (4) ◽  
pp. 614-624 ◽  
Author(s):  
Monika Weisz Hubshman ◽  
Sanne Broekman ◽  
Erwin van Wijk ◽  
Frans Cremers ◽  
Alaa Abu-Diab ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Recessive ◽  
Novel Gene ◽  
Whole Exome

scholarly journals Identification of a novel pathogenic missense mutation in PRPF31 using whole exome sequencing: a case report

2018 ◽  
Vol 103 (6) ◽  
pp. 761-767 ◽  
Author(s):  
Laura Bryant ◽  
Olga Lozynska ◽  
Anson Marsh ◽  
Tyler E Papp ◽  
Lucas van Gorder ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Missense Mutation ◽  
Whole Exome Sequencing ◽  
Protein Trafficking ◽  
Protein Misfolding ◽  
Autosomal Dominant ◽  
Null Alleles ◽  
Incomplete Penetrance ◽  
Missense Mutations ◽  
Whole Exome

BackgroundVariants in PRPF31, which encodes pre-mRNA processing factor 31 homolog, are known to cause autosomal-dominant retinitis pigmentosa (adRP) with incomplete penetrance. However, the majority of mutations cause null alleles, with only two proven pathogenic missense mutations. We identified a novel missense mutation in PRPF31 in a family with adRP.MethodsWe performed whole exome sequencing to identify possible pathogenic mutations in the proband of a family with adRP. Available affected family members had a full ophthalmological evaluation including kinetic and two-colour dark adapted static perimetry, electroretinography and multimodal imaging of the retina. Two patients had evaluations covering nearly 20 years. We carried out segregation analysis of the probable mutation, PRPF31 c.590T>C. We evaluated the cellular localisation of the PRPF31 variant (p.Leu197Pro) compared with the wildtype PRPF31 protein.ResultsPRPF31 c.590T>C segregated with the disease in this four-generation autosomal dominant pedigree. There was intrafamilial variability in disease severity. Nyctalopia and mid-peripheral scotomas presented from the second to the fourth decade of life. There was severe rod >cone dysfunction. Visual acuity (VA) was relatively intact and was maintained until later in life, although with marked interocular asymmetries. Laboratory studies showed that the mutant PRPF31 protein (p.Leu197Pro) does not localise to the nucleus, unlike the wildtype PRPF31 protein. Instead, mutant protein resulted in punctate localisation to the cytoplasm.Conclusionsc.590T>C is a novel pathogenic variant in PRPF31 causing adRP with incomplete penetrance. Disease may be due to protein misfolding and associated abnormal protein trafficking to the nucleus.

Whole exome sequencing identified a second pathogenic variant in HOMER2 for autosomal dominant non-syndromic deafness

2018 ◽  
Vol 94 (5) ◽  
pp. 419-428 ◽  
Author(s):  
X. Lu ◽  
Q. Wang ◽  
H. Gu ◽  
X. Zhang ◽  
Y. Qi ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Dominant ◽  
Pathogenic Variant ◽  
Whole Exome

scholarly journals Whole-Exome Sequencing Links a Variant in DHDDS to Retinitis Pigmentosa

2011 ◽  
Vol 88 (2) ◽  
pp. 201-206 ◽  
Author(s):  
Stephan Züchner ◽  
Julia Dallman ◽  
Rong Wen ◽  
Gary Beecham ◽  
Adam Naj ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Whole Exome

scholarly journals RHOMutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Satoshi Katagiri ◽  
Takaaki Hayashi ◽  
Masakazu Akahori ◽  
Takeshi Itabashi ◽  
Jo Nishino ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Retinitis Pigmentosa ◽  
Autosomal Dominant ◽  
Conformational Transition ◽  
Novel Mutation ◽  
The Novel ◽  
Autosomal Dominant Retinitis Pigmentosa ◽  
Modeling Analysis ◽  
Whole Exome ◽  
The Impact

Purpose. To investigate genetic and clinical features of patients with rhodopsin (RHO) mutations in two Japanese families with autosomal dominant retinitis pigmentosa (adRP).Methods. Whole-exome sequence analysis was performed in ten adRP families. IdentifiedRHOmutations for the cosegregation analysis were confirmed by Sanger sequencing. Ophthalmic examinations were performed to evaluate the RP phenotypes. The impact of theRHOmutation on the rhodopsin conformation was examined by molecular modeling analysis.Results. In two adRP families, we identified twoRHOmutations (c.377G>T (p.W126L) and c.1036G>C (p.A346P)), one of which was novel. Complete cosegregation was confirmed for each mutation exhibiting the RP phenotype in both families. Molecular modeling predicted that the novel mutation (p.W126L) might impair rhodopsin function by affecting its conformational transition in the light-adapted form. Clinical phenotypes showed that patients with p.W126L exhibited sector RP, whereas patients with p.A346P exhibited classic RP.Conclusions. Our findings demonstrated that the novel mutation (p.W126L) may be associated with the phenotype of sector RP. Identification ofRHOmutations is a very useful tool for predicting disease severity and providing precise genetic counseling.

scholarly journals Erratum: A dominant mutation in RPE65 identified by whole-exome sequencing causes retinitis pigmentosa with choroidal involvement

2011 ◽  
Vol 19 (10) ◽  
pp. 1109-1109
Author(s):  
Sara J Bowne ◽  
Marian M Humphries ◽  
Lori S Sullivan ◽  
Paul F Kenna ◽  
Lawrence CS Tam ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Dominant Mutation ◽  
Whole Exome
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