Results 141 to 150 of about 133,000 (265)

Kcnv2 E151X Mouse Captures Hallmarks of KCNV2‐Associated Retinal Dystrophy

Clinical &Experimental Ophthalmology, EarlyView.
ABSTRACT Background KCNV2‐associated retinopathy is a rare inherited retinal dystrophy caused by variants in the KCNV2 gene, leading to disrupted photoreceptor behaviour and progressive deterioration of vision. Patients have characteristic electroretinography abnormalities, including reduced cone response, delayed and reduced rod response to low light ...
Nermina Xhaferri, Sumit Biswas, Benjamin Davies, Moritz Lindner   +3 more
wiley   +1 more source

Identification of Copy Number Variants as a Suspected Cause of Cerebral Small Vessel Disease

Clinical Genetics, EarlyView.
Whole‐exome sequencing of 111 patients with suspected familial cerebral small vessel disease (CSVD) identified novel copy number variants in four patients across NOTCH3, LMNB1, and COL4A2, using bioinformatic and molecular techniques. These validated CNVs suggest structural variation is an underrecognized potential causal contributor to monogenic CSVD ...
Solomon K. Guyler, Neven Maksemous, Rodney A. Lea, Robert A. Smith, Heidi G. Sutherland, Lyn R. Griffiths   +5 more
wiley   +1 more source

Pathogenicity of NUSAP1 Variants Is Defined by NMD‐Escape: Evidence From Two Novel Cases and Systematic Population‐Based Variant Analysis

Clinical Genetics, EarlyView.
Heterozygous de novo nonsense variants in the penultimate and last exons of NUSAP1 were identified in two unrelated individuals, predicted to escape NMD. In population data, nonsense variants were observed in exons 1–9 (of 11) in NUSAP1 but were absent from its 3′‐terminal region.
Maureen Jacob, Susann Badmann, Stefania Bigoni, Maria Iascone, Ilaria Vivaldi, Katharina Mayerhanser, Robert Kopajtich, Holger Prokisch, Cristina Forest, Sebastian Eck, Michael Zech, Elisabeth Graf, Matias Wagner, Juliane Winkelmann, Theresa Brunet, Melanie Brugger   +15 more
wiley   +1 more source

A Homozygous Frameshift Variant in KHDC4 Is Associated With a Syndromic Inherited Retinal Disease in Humans

Clinical Genetics, EarlyView.
We identified a homozygous frameshift variant in KHDC4 (c.1535_1538del: (p.Lys512Argfs*8) in a consanguineous family with syndromic Retinitis Pigmentosa. Functional characterization shows aberrant protein mislocalisation from nuclear speckles to a diffuse pattern.
Asodu Sandeep Sarma, Neta Barnoy, Prakadeeswari Gopalakrishnan, Keren Dichter, Rotem Mizrachi, Manar Salameh, Eyal Banin, Dror Sharon, Adi Inbal, Samer Khateb   +9 more
wiley   +1 more source

Anticodon-edited tRNA enables translational readthrough of COL4A5 premature termination codons.

PLoS ONE
Alport syndrome is caused by variants in COL4A3, COL4A4, or COL4A5, which encode the α3α4α5 chains of type IV collagen. These variants result in defects in the glomerular basement membrane (GBM) and impaired kidney function.
Kohei Omachi, Joseph J Porter, John D Lueck, Jeffrey H Miner   +3 more
doaj   +1 more source

Investigation of premature termination codon recognition in nonsense-mediated mRNA decay

, 2014
Nonsense-mediated mRNA decay (NMD) is best known for its role in quality control of mRNAs, where it recognizes premature translation termination codons (PTCs) and rapidly degrades the corresponding mRNA. The basic mechanism of NMD appears to be conserved
Joncourt, Raphael
core  

A novel deep intronic EIF2AK3 variant disrupts splicing and causes Wolcott–Rallison syndrome

Diabetic Medicine, EarlyView.
Abstract Aim Deep intronic variants can disrupt splicing and cause monogenic disease but are missed by routine genetic testing. This study assessed the contribution of deep intronic variants to Wolcott–Rallison syndrome (WRS), a recessive disorder characterized by early‐onset diabetes and progressive multisystem disease caused by loss‐of‐function ...
Alaa Al Assi, Georgia Bonfield, James Russ‐Silsby, Suhel Ahmed, Thomas W. Laver, Kadri Karaer, Bayram Özhan, Ayca Altincik, Kashyap A. Patel, Jayne A. L. Houghton, Sarah E. Flanagan, Matthew B. Johnson, Elisa De Franco   +12 more
wiley   +1 more source

Blocking protein quality control degradation leads to structural stabilization of DHFR indel variants

The FEBS Journal, EarlyView.
Blocking protein quality control degradation by deleting the E3 ligases Ubr1 or San1 stabilizes many DHFR insertion and deletion variants that are otherwise partially unfolded. These hypomorphic variants regain folding at lower temperatures or upon methotrexate binding, revealing that PQC degradation can remove proteins that are still functionally ...
Sven Larsen‐Ledet, Caroline H. Suhr, Sarah Gersing, Celeste M. Hackney, Amelie Stein, Kaare Teilum, Rasmus Hartmann‐Petersen   +6 more
wiley   +1 more source

Directional information flow in human frataxin defines allosteric pathways connecting the hydrophobic core to the iron‐binding ridge

The FEBS Journal, EarlyView.
Human frataxin deficiency causes Friedreich's ataxia, yet how iron‐binding events are communicated across the protein is unclear. Using transfer entropy analysis of molecular dynamics simulations, we identify buried hydrophobic core leucines (LEU136, LEU140) as the source of directional signaling toward the iron‐binding acidic ridge.
Kevser Kübra Kırboğa, Ecir Uğur Küçüksille   +1 more
wiley   +1 more source

Newly identified human aminoacyl‐tRNA synthetase complex interacting multifunctional protein 2 (AIMP2) loss‐of‐function mutations cause neurodevelopmental defects linked to cell death in a zebrafish model

The FEBS Journal, EarlyView.
Human AIMP2 mutations lead to severe neurodevelopmental defects and brain atrophy. Using patient‐derived fibroblasts from two individuals, we show decreased AIMP2 protein levels and overall protein synthesis. In a zebrafish loss‐of‐function model, the lack of AIMP2 leads to an increase in cell death and results in smaller brains.
Patrick Mullen, Shenela Lakhani, Joshua Appelbaum, DéJenaé See, Pryce Patterson, Collin M. MacLeod, Alexandra George, Reza Maroofian, Margaret E. Ross, Christopher Francklyn, Alicia M. Ebert   +10 more
wiley   +1 more source