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showing 10 items of 10618 documents
Benign nocturnal alternating hemiplegia of childhood
2018
Objective: To describe the clinical spectrum of benign nocturnal alternating hemiplegia of childhood (BNAHC) including long-term follow-up data of previously published cases and to propose an underlying genetic cause of this disorder. Methods: We studied the medical data of two novel patients, reviewed the literature on BNAHC, and gathered information of the most recent follow-up of published cases regarding the course of episodes, further development, attempted drugs, ancillary investigations, and sequelae. Results: All patients, i.e. two novel cases and twelve patients identified in the literature (13 boys, 1 girl, age at onset four months to three years), experienced episodes of hemipleg…
The Commensal Microbiota Enhances ADP-Triggered Integrin αIIbβ3 Activation and von Willebrand Factor-Mediated Platelet Deposition to Type I Collagen
2020
The commensal microbiota is a recognized enhancer of arterial thrombus growth. While several studies have demonstrated the prothrombotic role of the gut microbiota, the molecular mechanisms promoting arterial thrombus growth are still under debate. Here, we demonstrate that germ-free (GF) mice, which from birth lack colonization with a gut microbiota, show diminished static deposition of washed platelets to type I collagen compared with their conventionally raised (CONV-R) counterparts. Flow cytometry experiments revealed that platelets from GF mice show diminished activation of the integrin αIIbβ3 (glycoprotein IIbIIIa) when activated by the platelet agonist adenosine diphosphate (ADP). Fu…
Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival
2019
Genomic instability pathways in colorectal cancer (CRC) have been extensively studied, but the role of retrotransposition in colorectal carcinogenesis remains poorly understood. Although retrotransposons are usually repressed, they become active in several human cancers, in particular those of the gastrointestinal tract. Here we characterize retrotransposon insertions in 202 colorectal tumor whole genomes and investigate their associations with molecular and clinical characteristics. We find highly variable retrotransposon activity among tumors and identify recurrent insertions in 15 known cancer genes. In approximately 1% of the cases we identify insertions in APC, likely to be tumor-initi…
IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients.
2019
Variants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy in males and females. We aimed to investigate sex-specific differences.
Interferon-γ-Driven iNOS: A Molecular Pathway to Terminal Shock in Arenavirus Hemorrhagic Fever
2017
Arenaviruses such as Lassa virus (LASV) cause hemorrhagic fever. Terminal shock is associated with a systemic cytokine storm, but the mechanisms are ill defined. Here we used HLA-A2-expressing mice infected with a monkey-pathogenic strain of lymphocytic choriomeningitis virus (LCMV-WE), a close relative of LASV, to investigate the pathophysiology of arenavirus hemorrhagic fever (AHF). AHF manifested as pleural effusions, edematous skin swelling, and serum albumin loss, culminating in hypovolemic shock. A characteristic cytokine storm included numerous pro-inflammatory cytokines and nitric oxide (NO) metabolites. Edema formation and terminal shock were abrogated in mice lacking inducible nit…
Clinical and biochemical characteristics of individuals with low cholesterol syndromes: A comparison between familial hypobetalipoproteinemia and fam…
2017
Background The most frequent monogenic causes of low plasma cholesterol are familial hypobetalipoproteinemia (FHBL1) because of truncating mutations in apolipoprotein B coding gene (APOB) and familial combined hypolipidemia (FHBL2) due to loss-of-function mutations in ANGPTL3 gene. Objective A direct comparison of lipid phenotypes of these 2 conditions has never been carried out. In addition, although an increased prevalence of liver steatosis in FHBL1 has been consistently reported, the hepatic consequences of FHBL2 are not well established. Methods We investigated 350 subjects, 67 heterozygous carriers of APOB mutations, 63 carriers of the p.S17* mutation in ANGPTL3 (57 heterozygotes and …
Expression quantitative trait loci for PAX8 contributes to the prognosis of hepatocellular carcinoma
2017
Paired-box family member PAX8 encodes a transcription factor that has a role in cell differentiation and cell growth and may participate in the prognosis of hepatocellular carcinoma (HCC). By bioinformatics analysis, we identified several single nucleotide polymorphisms (SNPs) within a newly identified long non-coding RNA (lncRNA) AC016683.6 as expression quantitative trait loci (eQTLs) for PAX8. Hence, we hypothesized that PAX8eQTLs in lncRNA AC016683.6 may influence the HCC prognosis. We then performed a case-only study to assess the association between the two SNPs as well as the prognosis of HCC in 331 HBV-positive HCC patients without surgical treatment. Cox proportional hazard models …
Generation of a disease-specific iPS cell line derived from a patient with Charcot-Marie-Tooth type 2K lacking functional GDAP1 gene
2016
Human CMT2-FiPS4F1 cell line was generated from fibroblasts of a patient with Charcot-Marie-Tooth disease harbouring the following mutations in the GDAP1 gene in heterozygosis: p.Q163X/p.T288NfsX3. This patient did not present mutations in the PM22, MPZ or GJB genes. Human reprogramming factors OCT3/4, KLF4, SOX2 and C-MYC were delivered using a non-integrative methodology that involves the use of Sendai virus.
The Effect of a Novel c.820C>T (Arg274Trp) Mutation in the Mitofusin 2 Gene on Fibroblast Metabolism and Clinical Manifestation in a Patient
2017
Charcot-Marie-Tooth disease type 2A (CMT2A) is an autosomal dominant axonal peripheral neuropathy caused by mutations in the mitofusin 2 gene (MFN2). Mitofusin 2 is a GTPase protein present in the outer mitochondrial membrane and responsible for regulation of mitochondrial network architecture via the fusion of mitochondria. As that fusion process is known to be strongly dependent on the GTPase activity of mitofusin 2, it is postulated that the MFN2 mutation within the GTPase domain may lead to impaired GTPase activity, and in turn to mitochondrial dysfunction. The work described here has therefore sought to verify the effects of MFN2 mutation within its GTPase domain on mitochondrial and e…
Protective and causative killer Ig-like receptor (KIR) and metalloproteinase genetic patterns associated with Herpes simplex virus 1 (HSV-1) encephal…
2020
Abstract Background The cerebral innate immune system has a critical role in control processes of viral replication in the brain after primary infactivo and immunologic disregulation and inflammation has been reported as a primary determinant of pathogenesis and prognosis of subsequent HSV-1 related encephalitis (HSE). Interaction linking LTR3-activated DCs is also represented by the killer Ig-like receptor (KIR) + pathways on NK cells. Only a few studies analyzed the role of of MMP-9 activity regulating genetic polymorphism on clinical outcome of viral infections. Susceptibility to symptomatic encephalitis depends on SNC viral invasion and BBB disruption. We hypothesize that certain KIR ge…