Generation of three isogenic induced Pluripotent Stem Cell lines (iPSCs) from fibroblasts of a patient with Aicardi Goutières Syndrome carrying a c.2471G>A dominant mutation in IFIH1 gene

Publication date: Available online 22 October 2019Source: Stem Cell ResearchAuthor(s): S Masneri, G Lanzi, RM Ferraro, C Barisani, G Piovani, G Savio, M Cattalini, J Galli, C Cereda, M Muzi-Falconi, S Orcesi, E Fazzi, S GilianiAbstractAicardi-Goutières syndrome (AGS) is an early-onset monogenic encephalopathy characterized by intracranial calcification, leukodystrophy and cerebrospinal fluid lymphocytosis. To date, seven genes have been related to AGS. Among these, IFIH1 encodes for MDA5, a cytosolic double-stranded RNA receptor, and is responsible for AGS type7. We generated three isogenic iPSC clones, using a Sendai virus-based vector, starting from fibroblasts of a patient carrying a dominant mutation in IFIH1. All lines were characterized for genomic integrity, genetic uniqueness, pluripotency, and differentiation capability. Our clones might offer a good model to investigate AGS7 pathophysiological mechanism and to discover new biomarkers for this condition treatment.
Source: Stem Cell Research - Category: Stem Cells Source Type: research

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Authors: Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR Abstract Introduction: Leukodystrophies constitute heterogenous group of rare heritable disorders primarily affecting the white matter of central nervous system. These conditions are often under-appreciated among physicians. The first clinical manifestations of leukodystrophies are often nonspecific and can occur in different ages from neonatal to late adulthood periods. The diagnosis is, therefore, challenging in most cases.Area covered: Herein, the authors discuss different aspects of leukodystrophies. The authors used...
Source: Expert Review of Neurotherapeutics - Category: Neurology Tags: Expert Rev Neurother Source Type: research
Abstract Pelizaeus-Merzbacher disease (PMD) is an X-linked leukodystrophy caused by mutations in Proteolipid Protein 1 (PLP1), encoding a major myelin protein, resulting in profound developmental delay and early lethality. Previous work showed involvement of unfolded protein response (UPR) and endoplasmic reticulum (ER) stress pathways, but poor PLP1 genotype-phenotype associations suggest additional pathogenetic mechanisms. Using induced pluripotent stem cell (iPSC) and gene-correction, we show that patient-derived oligodendrocytes can develop to the pre-myelinating stage, but subsequently undergo cell death. Mut...
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research
The leukodystrophies are a heterogeneous group of inherited disorders that disrupt myelination in the central nervous system (CNS) and may also involve the peripheral nervous system. The onset and severity of symptoms differ between diseases and may correlate with genetic mutation(s). In the most severe forms, affected individuals experience rapid, progressive, and ultimately fatal neurologic symptoms. Without newborn screening (NBS) or a known family history, the diagnosis of the index case in a family is usually delayed until symptoms are present and progress to a stage where treatment with transplantation is no longer p...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Publication date: Available online 1 August 2019Source: Stem Cell ReportsAuthor(s): Nalin Gupta, Roland G. Henry, Sang-Mo Kang, Jonathan Strober, Daniel A. Lim, Tamara Ryan, Rachel Perry, Jody Farrell, Mary Ulman, Raja Rajalingam, Allyson Gage, Stephen L. Huhn, A. James Barkovich, David H. RowitchSummaryFour boys with Pelizaeus-Merzbacher disease, an X-linked leukodystrophy, underwent transplantation with human allogeneic central nervous system stem cells (HuCNS-SC). Subsequently, all subjects were followed for an additional 4 years in this separate follow-up study to evaluate safety, neurologic function, magnetic resonanc...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
CONCLUSIONS: Although the complication rate for patients with Krabbe disease and metachromatic leukodystrophy is higher than the general population, most complications were mild and self-limiting. These results suggest that, in experienced hands, general anesthesia is well tolerated in most children. Findings show that the Neurodevelopment in Rare Disorders classification system is a better indicator for assessing complication risk in patients with Krabbe and metachromatic leukodystrophy than American Society of Anesthesiologists Physical Status. PMID: 31359511 [PubMed - as supplied by publisher]
Source: Paediatric Anaesthesia - Category: Anesthesiology Authors: Tags: Paediatr Anaesth Source Type: research
Neuropediatrics DOI: 10.1055/s-0039-1685529Leukodystrophies (LDs) predominantly affect the white matter of the central nervous system and its main component, the myelin. The majority of LDs manifests in infancy with progressive neurodegeneration. Main clinical signs are intellectual and motor function losses of already attained developmental skills. Classical LDs include lysosomal storage disorders like metachromatic leukodystrophy (MLD), peroxisomal disorders like X-linked adrenoleukodystrophy (X-ALD), disorders of mitochondrial dysfunction, and myelin protein defects like Pelizaeus-Merzbacher disease. So far, there are o...
Source: Neuropediatrics - Category: Neurology Authors: Tags: Review Article Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 21 February 2019Source: Stem Cell ReportsAuthor(s): Stephanie Dooves, Prisca S. Leferink, Sander Krabbenborg, Nicole Breeuwsma, Saskia Bots, Anne E.J. Hillen, Gerbren Jacobs, Marjo S. van der Knaap, Vivi M. HeineSummaryStem cell therapy has great prospects for brain white matter disorders, including the genetically determined disorders called leukodystrophies. We focus on the devastating leukodystrophy vanishing white matter (VWM). Patients with VWM show severe disability and early death, and treatment options are lacking. Previous studies showed successful cell replacement therapy in rod...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
Mucopolysaccharidosis type IH (MPS1/Hurler Syndrome), cerebral adrenoleukodystrophy (cALD), metachromatic leukodystrophy (MLD) and globoid cell leukodystrophy (GLD) are fatal IMDs affecting the central nervous system treatable through allogeneic hematopoietic stem cell transplantation (HSCT). In the absence of a non-carrier HLA matched related donor, cord blood (CB) is the preferred source of cells in IMDs due to rapid availability and flexibility in matching. However, prolonged neutropenia and high graft failure rates present a challenge, particularly with reduced intensity conditioning regimens.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 122 Source Type: research
In conclusion, we found a gradient of increasing blood pressure with higher levels of BMI. The fact that this gradient is present even in the fully adjusted analyses suggests that BMI may cause a direct effect on blood pressure, independent of other clinical risk factors. PRRX1 as a Possible Point of Control for Remyelination https://www.fightaging.org/archives/2018/12/prrx1-as-a-possible-point-of-control-for-remyelination/ Researchers here outline what is possibly a new point of intervention in the processes that maintain the myelin sheath that wraps nerves. This sheath is vital to the correct operatio...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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