Bilateral striatal necrosis and dyschromatosis symmetrica hereditaria: A-I editing efficiency of ADAR1 mutants and phenotype expression

2018 ◽  
Author(s):  
M. Kono ◽  
M. Suganuma ◽  
A. Dutta ◽  
S.K. Ghosh ◽  
T. Takeichi ◽  
...  
Keyword(s):  
Editing Efficiency ◽  
Dyschromatosis Symmetrica Hereditaria ◽  
Phenotype Expression ◽  
Striatal Necrosis

Variable Phenotype Expression of a Maternally Inherited 16P13.11 Deletion in Twin Brothers with Epilepsy

2018 ◽  
Vol 49 (S 01) ◽  
pp. S1-S12
Author(s):  
M. Sallemi ◽  
S. Gambara ◽  
J. Galli ◽  
E. Fazzi
Keyword(s):  
Variable Phenotype ◽  
Phenotype Expression

Bilateral Striatal Necrosis with Polyneuropathy with a Novel SLC25A19 (Mitochondrial Thiamine Pyrophosphate Carrier OMIMI*606521) Mutation: Treatable Thiamine Metabolic Disorder—A Report of Two Indian Cases

2019 ◽  
Vol 50 (05) ◽  
pp. 313-317 ◽  
Author(s):  
Vykuntaraju K. Gowda ◽  
Varunvenkat M. Srinivasan ◽  
Kapil Jehta ◽  
Maya D. Bhat
Keyword(s):  
Gene Mutations ◽  
Febrile Illness ◽  
Flaccid Paralysis ◽  
Thiamine Pyrophosphate ◽  
Homozygous Mutation ◽  
Missense Variation ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain ◽  
Generation Sequencing ◽  
Striatal Necrosis

Abstract Background SLC25A19 gene mutations cause Amish congenital lethal microcephaly and bilateral striatal necrosis with polyneuropathy. We are reporting two cases of bilateral striatal necrosis with polyneuropathy due to SLC25A19 gene mutations. Methods A 36-month-old boy and a 5-year-old girl, unrelated, presented with recurrent episodes of flaccid paralysis and encephalopathy following nonspecific febrile illness. Examination showed dystonia and absent deep tendon reflexes. Results Nerve conduction studies showed an axonal polyneuropathy. Magnetic resonance imaging (MRI) of the brain in both cases showed signal changes in the basal ganglia. Next-generation sequencing revealed a novel homozygous missense variation c.910G>A (p.Glu304Lys) in the SLC25A19 gene in the boy and a homozygous mutation c.869T > A (p. Leu290Gln) in the SLC25A19 gene in the girl. Mutations were validated by Sanger sequencing, and carrier statuses of parents of both children were confirmed. Both children improved with thiamine supplementation. Conclusion If any child presents with recurrent encephalopathy with flaccid paralysis, dystonia, and neuropathy, a diagnosis of bilateral striatal necrosis with polyneuropathy due to SLC25A19 mutations should be considered and thiamine should be initiated.

scholarly journals Efficient Peptide-Mediated In Vitro Delivery of Cas9 RNP

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 878
Author(s):  
Oskar Gustafsson ◽  
Julia Rädler ◽  
Samantha Roudi ◽  
Tõnis Lehto ◽  
Mattias Hällbrink ◽  
...  
Keyword(s):  
Freeze Drying ◽  
Cell Penetrating Peptide ◽  
Wild Type ◽  
Efficient Manner ◽  
Editing Efficiency ◽  
Freeze Thaw ◽  
Enzyme Digest ◽  
Clinical Potential ◽  
Generation Sequencing

The toolbox for genetic engineering has quickly evolved from CRISPR/Cas9 to a myriad of different gene editors, each with promising properties and enormous clinical potential. However, a major challenge remains: delivering the CRISPR machinery to the nucleus of recipient cells in a nontoxic and efficient manner. In this article, we repurpose an RNA-delivering cell-penetrating peptide, PepFect14 (PF14), to deliver Cas9 ribonucleoprotein (RNP). The RNP-CPP complex achieved high editing rates, e.g., up to 80% in HEK293T cells, while being active at low nanomolar ranges without any apparent signs of toxicity. The editing efficiency was similar to or better compared to the commercially available reagents RNAiMAX and CRISPRMax. The efficiency was thoroughly evaluated in reporter cells and wild-type cells by restriction enzyme digest and next-generation sequencing. Furthermore, the CPP-Cas9-RNP complexes were demonstrated to withstand storage at different conditions, including freeze-thaw cycles and freeze-drying, without a loss in editing efficiency. This CPP-based delivery strategy complements existing technologies and further opens up new opportunities for Cas9 RNP delivery, which can likely be extended to other gene editors in the future.

SLC25A19 deficiency and bilateral striatal necrosis with polyneuropathy: a new case and review of the literature

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Francesco Porta ◽  
Barbara Siri ◽  
Nicoletta Chiesa ◽  
Federica Ricci ◽  
Lulash Nika ◽  
...  
Keyword(s):  
Axonal Neuropathy ◽  
Clinical Signs ◽  
Leigh Syndrome ◽  
High Dose ◽  
New Variant ◽  
Long Term Follow Up ◽  
Basal Ganglia Involvement ◽  
Biallelic Mutations ◽  
Thiamine Treatment ◽  
Striatal Necrosis

AbstractObjectivesBiallelic mutations in the SLC25A19 gene impair the function of the thiamine mitochondrial carrier, leading to two distinct clinical phenotypes. Homozygosity for the c.530G > C mutation is invariably associated to Amish lethal microcephaly. The second phenotype, reported only in 8 patients homozygous for different non-Amish mutations (c.373G > A, c.580T > C, c.910G > A, c.869T > A, c.576G > C), is characterized by bilateral striatal necrosis and peripheral polyneuropathy. We report a new patient with the non-Amish SLC25A19 phenotype showing compound heterozygosity for the new variant c.673G > A and the known mutation c.373G > A.Case presentationThe natural history of non-Amish SLC25A19 deficiency is characterized by acute episodes of fever-induced encephalopathy accompanied by isolated lactic acidosis and Leigh-like features at magnetic resonance imaging (MRI). Acute episodes are prevented by high-dose thiamine treatment (600 mg/day). As shown in the new case, both mild clinical signs and basal ganglia involvement can precede the acute encephalopathic onset of the disease, potentially allowing treatment anticipation and prevention of acute brain damage. Peripheral axonal neuropathy, observed in 7 out of 9 patients, is not improved by thiamine therapy. In two early treated patients, however, peripheral neuropathy did not occur even on long-term follow-up, suggesting a potential preventive role of treatment anticipation also at the peripheral level.ConclusionsNon-Amish SLC25A19 deficiency is an extra-rare cause of Leigh syndrome responsive to thiamine treatment. Ex adiuvantibus thiamine treatment is mandatory in any patient with Leigh-like features.

scholarly journals Validation of gene editing efficiency with CRISPR-Cas9 system directly in rat zygotes using electroporationmediated delivery and embryo culture

MethodsX ◽  
2021 ◽  
pp. 101419
Author(s):  
Anil K Challa ◽  
Denise Stanford ◽  
Antonio Allen ◽  
Lawrence Rasmussen ◽  
Ferdinand K Amanor ◽  
...  
Keyword(s):  
Embryo Culture ◽  
Gene Editing ◽  
Editing Efficiency

scholarly journals AsCas12a ultra nuclease facilitates the rapid generation of therapeutic cell medicines

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Liyang Zhang ◽  
John A. Zuris ◽  
Ramya Viswanathan ◽  
Jasmine N. Edelstein ◽  
Rolf Turk ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Genome Editing ◽  
Nk Cell ◽  
Basic Research ◽  
Cell Recognition ◽  
Site Specific ◽  
Editing Efficiency ◽  
Rapid Generation ◽  
Therapeutic Cell

AbstractThough AsCas12a fills a crucial gap in the current genome editing toolbox, it exhibits relatively poor editing efficiency, restricting its overall utility. Here we isolate an engineered variant, “AsCas12a Ultra”, that increased editing efficiency to nearly 100% at all sites examined in HSPCs, iPSCs, T cells, and NK cells. We show that AsCas12a Ultra maintains high on-target specificity thereby mitigating the risk for off-target editing and making it ideal for complex therapeutic genome editing applications. We achieved simultaneous targeting of three clinically relevant genes in T cells at >90% efficiency and demonstrated transgene knock-in efficiencies of up to 60%. We demonstrate site-specific knock-in of a CAR in NK cells, which afforded enhanced anti-tumor NK cell recognition, potentially enabling the next generation of allogeneic cell-based therapies in oncology. AsCas12a Ultra is an advanced CRISPR nuclease with significant advantages in basic research and in the production of gene edited cell medicines.

scholarly journals Automated and Manual Data Editing: A View on Process Design and Methodology

2013 ◽  
Vol 29 (4) ◽  
pp. 511-537 ◽  
Author(s):  
Jeroen Pannekoek ◽  
Sander Scholtus ◽  
Mark Van der Loo
Keyword(s):  
Process Design ◽  
A Priori ◽  
Empirical Evaluation ◽  
Efficiency Gains ◽  
Specific Nature ◽  
Editing Efficiency ◽  
Data Editing ◽  
Optimal Mix ◽  
Editing Process ◽  
Statistical Functions

Abstract Data editing is arguably one of the most resource-intensive processes at NSIs. Forced by everincreasing budget pressure, NSIs keep searching for more efficient forms of data editing. Efficiency gains can be obtained by selective editing, that is, limiting the manual editing to influential errors, and by automating the editing process as much as possible. In our view, an optimal mix of these two strategies should be aimed for. In this article we present a decomposition of the overall editing process into a number of different tasks and give an upto- date overview of all the possibilities of automatic editing in terms of these tasks. During the design of an editing process, this decomposition may be helpful in deciding which tasks can be done automatically and for which tasks (additional) manual editing is required. Such decisions can be made a priori, based on the specific nature of the task, or by empirical evaluation, which is illustrated by examples. The decomposition in tasks, or statistical functions, also naturally leads to reuseable components, resulting in efficiency gains in process design.

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