A novel SLC2A1 mutation linking hemiplegic migraine with alternating hemiplegia of childhood

Cephalalgia ◽  
2014 ◽  
Vol 35 (1) ◽  
pp. 10-15 ◽  
Author(s):  
Claudia M Weller ◽  
Wilhelmina G Leen ◽  
Brian GR Neville ◽  
John S Duncan ◽  
Boukje de Vries ◽  
...  
Keyword(s):  
De Novo ◽  
The Other ◽  
Brain Disorders ◽  
Complex Phenotype ◽  
Hemiplegic Migraine ◽  
Alternating Hemiplegia Of Childhood ◽  
Genetic Overlap ◽  
Slc2a1 Gene ◽  
Small Set

Background Hemiplegic migraine (HM) and alternating hemiplegia of childhood (AHC) are rare episodic neurological brain disorders with partial clinical and genetic overlap. Recently, ATP1A3 mutations were shown to account for the majority of AHC patients. In addition, a mutation in the SLC2A1 gene was reported in a patient with atypical AHC. We therefore investigated whether mutations in these genes may also be involved in HM. Furthermore, we studied the role of SLC2A1 mutations in a small set of AHC patients without ATP1A3 mutations. Methods We screened 42 HM patients (21 familial and 21 sporadic patients) for ATP1A3 and SLC2A1 mutations. In addition, four typical AHC patients and one atypical patient with overlapping symptoms of both disorders were screened for SLC2A1 mutations. Results A pathogenic de novo SLC2A1 mutation (p.Gly18Arg) was found in the atypical patient with overlapping symptoms of AHC and hemiplegic migraine. No mutations were found in the HM and the other AHC patients. Conclusion Screening for a mutation in the SLC2A1 gene should be considered in patients with a complex phenotype with overlapping symptoms of hemiplegic migraine and AHC.

CACNA1A Mutation Linking Hemiplegic Migraine and Alternating Hemiplegia of Childhood

Cephalalgia ◽  
2008 ◽  
Vol 28 (8) ◽  
pp. 887-891 ◽  
Author(s):  
B de Vries ◽  
AH Stam ◽  
F Beker ◽  
AMJM van den Maagdenberg ◽  
KRJ Vanmolkot ◽  
...  
Keyword(s):  
Clinical Features ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Monozygotic Twin ◽  
Familial Hemiplegic Migraine ◽  
Hemiplegic Migraine ◽  
Mutation Scanning ◽  
Alternating Hemiplegia Of Childhood ◽  
Neurological Phenotype ◽  
Cacna1a Mutation

Familial hemiplegic migraine (FHM) and alternating hemiplegia of childhood (AHC) are severe neurological disorders that share clinical features. Therefore, FHM genes are candidates for AHC. We performed mutation analysis in the CACNA1A gene in a monozygotic twin pair with clinical features overlapping with both AHC and FHM and identified a novel de novo CACNA1A mutation. We provide the first evidence that a CACNA1A mutation can cause atypical AHC, indicating an overlap of molecular mechanisms causing AHC and FHM. These results also suggest that CACNA1A mutation scanning is indicated in patients with a severe neurological phenotype that includes paroxysmal (alternating) hemiplegia.

Patterning the dorsal longitudinal flight muscles (DLM) of Drosophila: insights from the ablation of larval scaffolds

Development ◽  
1996 ◽  
Vol 122 (12) ◽  
pp. 3755-3763 ◽  
Author(s):  
J.J. Fernandes ◽  
H. Keshishian
Keyword(s):  
Transcription Factor ◽  
De Novo ◽  
Muscle Fibers ◽  
Myoblast Fusion ◽  
The Other ◽  
Correct Number ◽  
Larval Muscle ◽  
Actin Isoform ◽  
Flight Muscles

The six Dorsal Longitudinal flight Muscles (DLMs) of Drosophila develop from three larval muscles that persist into metamorphosis and serve as scaffolds for the formation of the adult fibers. We have examined the effect of muscle scaffold ablation on the development of DLMs during metamorphosis. Using markers that are specific to muscle and myoblasts we show that in response to the ablation, myoblasts which would normally fuse with the larval muscle, fuse with each other instead, to generate the adult fibers in the appropriate regions of the thorax. The development of these de novo DLMs is delayed and is reflected in the delayed expression of erect wing, a transcription factor thought to control differentiation events associated with myoblast fusion. The newly arising muscles express the appropriate adult-specific Actin isoform (88F), indicating that they have the correct muscle identity. However, there are frequent errors in the number of muscle fibers generated. Ablation of the larval scaffolds for the DLMs has revealed an underlying potential of the DLM myoblasts to initiate de novo myogenesis in a manner that resembles the mode of formation of the Dorso-Ventral Muscles, DVMs, which are the other group of indirect flight muscles. Therefore, it appears that the use of larval scaffolds is a superimposition on a commonly used mechanism of myogenesis in Drosophila. Our results show that the role of the persistent larval muscles in muscle patterning involves the partitioning of DLM myoblasts, and in doing so, they regulate formation of the correct number of DLM fibers.

scholarly journals Strategies for acquiring the phospholipid metabolite inositol in pathogenic bacteria, fungi and protozoa: making it and taking it

Microbiology ◽  
2009 ◽  
Vol 155 (5) ◽  
pp. 1386-1396 ◽  
Author(s):  
Todd B. Reynolds
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Candida Albicans ◽  
Trypanosoma Brucei ◽  
Pathogenic Bacteria ◽  
De Novo ◽  
The Other ◽  
Inositol Monophosphatase ◽  
Essential Nutrient ◽  
Phosphate Synthase

myo-Inositol (inositol) is an essential nutrient that is used for building phosphatidylinositol and its derivatives in eukaryotes and even in some eubacteria such as the mycobacteria. As a consequence, fungal, protozoan and mycobacterial pathogens must be able to acquire inositol in order to proliferate and cause infection in their hosts. There are two primary mechanisms for acquiring inositol. One is to synthesize inositol from glucose 6-phosphate using two sequentially acting enzymes: inositol-3-phosphate synthase (Ino1p) converts glucose 6-phosphate to inositol 3-phosphate, and then inositol monophosphatase (IMPase) dephosphorylates inositol 3-phosphate to generate inositol. The other mechanism is to import inositol from the environment via inositol transporters. Inositol is readily abundant in the bloodstream of mammalian hosts, providing a source from which many pathogens could potentially import inositol. However, despite this abundance of inositol in the host, some pathogens such as the bacterium Mycobacterium tuberculosis and the protist parasite Trypanosoma brucei must be able to make inositol de novo in order to cause disease (M. tuberculosis) or even grow (T. brucei). Other pathogens such as the fungus Candida albicans are equally adept at causing disease by importing inositol or by making it de novo. The role of inositol acquisition in the biology and pathogenesis of the parasite Leishmania and the fungus Cryptococcus are being explored as well. The specific strategies used by these pathogens to acquire inositol while in the host are discussed in relation to each pathogen's unique metabolic requirements.

scholarly journals Importance of Trehalose Biosynthesis for Sinorhizobium meliloti Osmotolerance and Nodulation of Alfalfa Roots

2009 ◽  
Vol 191 (24) ◽  
pp. 7490-7499 ◽  
Author(s):  
Ana Domínguez-Ferreras ◽  
María J. Soto ◽  
Rebeca Pérez-Arnedo ◽  
José Olivares ◽  
Juan Sanjuán
Keyword(s):  
Sinorhizobium Meliloti ◽  
De Novo ◽  
The Other ◽  
Biosynthesis Pathway ◽  
De Novo Biosynthesis ◽  
Common Response ◽  
Trehalose Biosynthesis ◽  
Trehalose Synthesis ◽  
Trehalose Accumulation

ABSTRACT The disaccharide trehalose is a well-known osmoprotectant, and trehalose accumulation through de novo biosynthesis is a common response of bacteria to abiotic stress. In this study, we have investigated the role of endogenous trehalose synthesis in the osmotolerance of Sinorhizobium meliloti. Genes coding for three possible trehalose synthesis pathways are present in the genome of S. meliloti 1021: OtsA, TreYZ, and TreS. Among these, OtsA has a major role in trehalose accumulation under all of the conditions tested and is the main system involved in osmoadaptation. Nevertheless, the other two systems are also important for growth in hyperosmotic medium. Genes for the three pathways are transcriptionally responsive to osmotic stress. The presence of at least one functional trehalose biosynthesis pathway is required for optimal competitiveness of S. meliloti to nodulate alfalfa roots.

scholarly journals Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcription

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Feng ◽  
Yao Wang ◽  
Xiangnan Wang ◽  
Xiaohui He ◽  
Chen Yang ◽  
...  
Keyword(s):  
Genome Organization ◽  
Transcriptional Repression ◽  
De Novo ◽  
Active Regions ◽  
Gene Repression ◽  
Domain Formation ◽  
Transcriptional Initiation ◽  
Chromatin Architecture ◽  
Small Set

Abstract Introduction Despite the long-observed correlation between H3K9me3, chromatin architecture, and transcriptional repression, how H3K9me3 regulates genome higher-order organization and transcriptional activity in living cells remains unclear. Result Here, we develop EpiGo (Epigenetic perturbation induced Genome organization)-KRAB to introduce H3K9me3 at hundreds of loci spanning megabases on human chromosome 19 and simultaneously track genome organization. EpiGo-KRAB is sufficient to induce genomic clustering and de novo heterochromatin-like domain formation, which requires SETDB1, a methyltransferase of H3K9me3. Unexpectedly, EpiGo-KRAB-induced heterochromatin-like domain does not result in widespread gene repression except a small set of genes with concurrent loss of H3K4me3 and H3K27ac. Ectopic H3K9me3 appears to spread in inactive regions but is largely restricted from transcriptional initiation sites in active regions. Finally, Hi-C analysis showed that EpiGo-KRAB reshapes existing compartments mainly at compartment boundaries. Conclusions These results reveal the role of H3K9me3 in genome organization could be partially separated from its function in gene repression.

scholarly journals Simultaneous Epigenetic Perturbation and Genome Imaging Reveal Distinct Roles of H3K9me3 in Chromatin Architecture and Transcription

2020 ◽  
Author(s):  
Ying Feng ◽  
Yao Wang ◽  
Xiangnan Wang ◽  
Xiaohui He ◽  
Chen Yang ◽  
...  
Keyword(s):  
Genome Organization ◽  
Transcriptional Repression ◽  
De Novo ◽  
Active Regions ◽  
Gene Repression ◽  
Domain Formation ◽  
Transcriptional Initiation ◽  
Chromatin Architecture ◽  
Small Set

AbstractDespite the long-observed correlation between H3K9me3, chromatin architecture and transcriptional repression, how H3K9me3 regulates genome higher-order organization and transcriptional activity in living cells remains unclear. Here we develop EpiGo (Epigenetic perturbation induced Genome organization)-KRAB to introduce H3K9me3 at hundreds of loci spanning megabases on human chromosome 19 and simultaneously track genome organization. EpiGo-KRAB is sufficient to induce de novo heterochromatin-like domain formation, which requires SETDB1, a methyltransferase of H3K9me3. Unexpectedly, EpiGo-KRAB induced heterochromatin-like domain does not result in widespread gene repression except a small set of genes with concurrent loss of H3K4me3 and H3K27ac. Ectopic H3K9me3 appears to spread in inactive regions but is largely restricted to transcriptional initiation sites in active regions. Finally, Hi-C analysis showed that EpiGo-KRAB induced to reshape existing compartments. These results reveal the role of H3K9me3 in genome organization could be partially separated from its function in gene repression.

scholarly journals A case report of atypical hemiplegic migraine with nonheadache onset in a Chinese child

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hui Chen ◽  
Xiaolan Sun ◽  
Ruiyan Wang ◽  
Zhaoshi Yi ◽  
Zhixin Huang ◽  
...  
Keyword(s):  
De Novo ◽  
Chinese Child ◽  
Hemiplegic Migraine ◽  
Motor Weakness ◽  
Alternating Hemiplegia Of Childhood ◽  
Whole Exome ◽  
Initial Stage ◽  
Atp1a2 Gene ◽  
Magnetic Resonance Imaging Mri ◽  
Core Symptoms

Abstract Background Hemiplegic migraine (HM) is an uncommon subtype of migraine with aura including motor weakness. The core symptoms of HM are headache and motor weakness. However, we report a rare case of atypical HM with nonheadache onset in a Chinese child who was misdiagnosed several times. Case presentation We report a Chinese boy whose onset was sudden when he was 3 years old. He presented with a variety of phenotypes, including fever, vomiting, alternating hemiplegia, and drowsiness, but no headache in the initial stages. Magnetic resonance imaging (MRI) demonstrated unilateral cerebral oedema during the initial episode of hemiplegia. These symptoms recurred many times. As the disease progressed, the patient developed episodic headache. The patient was misdiagnosed several times with encephalitis, alternating hemiplegia of childhood (AHC) and mitochondrial encephalopathy. Whole-exome next-generation sequencing revealed a de novo heterozygous missense mutation in the ATP1A2 gene(p.Gly715Arg) classified as pathogenic and eventually led to a diagnosis of HM when he was 11 years old. Flunarizine was subsequently administered, and no recurrence was found during follow-up. Conclusions HM in children may be atypical in the initial stage of the disease, which could manifest as fever, alternating hemiplegia and drowsiness but no headache at the onset. This could easily lead to misdiagnosis. With age, it may eventually manifest as typical HM. Therefore, attention should be given to differentiation in clinical practice.When similar clinical cases appear, gene detection is particularly important, which is conducive to early diagnosis and treatment.

Posttransplant CMV infection and the role of immunosuppression (Sponsor: Novartis Pharma GmbH, Nürnberg)

2016 ◽  
Vol 04 (01) ◽  
pp. 4-10
Keyword(s):  
Lower Incidence ◽  
Paradigm Shift ◽  
Mtor Inhibitor ◽  
De Novo ◽  
Expert Panel ◽  
Risk Of Infection ◽  
Cmv Infection ◽  
Expert Meeting ◽  
Selection Of

AbstractImmunosuppression permits graft survival after transplantation and consequently a longer and better life. On the other hand, it increases the risk of infection, for instance with cytomegalovirus (CMV). However, the various available immunosuppressive therapies differ in this regard. One of the first clinical trials using de novo everolimus after kidney transplantation [1] already revealed a considerably lower incidence of CMV infection in the everolimus arms than in the mycophenolate mofetil (MMF) arm. This result was repeatedly confirmed in later studies [2–4]. Everolimus is now considered a substance with antiviral properties. This article is based on the expert meeting “Posttransplant CMV infection and the role of immunosuppression”. The expert panel called for a paradigm shift: In a CMV prevention strategy the targeted selection of the immunosuppressive therapy is also a key element. For patients with elevated risk of CMV, mTOR inhibitor-based immunosuppression is advantageous as it is associated with a significantly lower incidence of CMV events.

Plasma Levels of Protein S, Protein C, and Factor X: Effects of Sex, Hormonal State and Age

1995 ◽  
Vol 74 (05) ◽  
pp. 1271-1275 ◽  
Author(s):  
C M A Henkens ◽  
V J J Bom ◽  
W van der Schaaf ◽  
P M Pelsma ◽  
C Th Smit Sibinga ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Postmenopausal Women ◽  
Protein C ◽  
Blood Donors ◽  
Premenopausal Women ◽  
Protein S ◽  
The Other ◽  
Factor X ◽  
Normal Ranges

SummaryWe measured total and free protein S (PS), protein C (PC) and factor X (FX) in 393 healthy blood donors to assess differences in relation to sex, hormonal state and age. All measured proteins were lower in women as compared to men, as were levels in premenopausal women as compared to postmenopausal women. Multiple regression analysis showed that both age and subgroup (men, pre- and postmenopausal women) were of significance for the levels of total and free PS and PC, the subgroup effect being caused by the differences between the premenopausal women and the other groups. This indicates a role of sex-hormones, most likely estrogens, in the regulation of levels of pro- and anticoagulant factors under physiologic conditions. These differences should be taken into account in daily clinical practice and may necessitate different normal ranges for men, pre- and postmenopausal women.

On the role of the dispute between "non-possessors" and "Josephites" in the culture of Moscow's prediction

1998 ◽  
pp. 61-62
Author(s):  
N. S. Jurtueva
Keyword(s):  
The Other ◽  
Moral Transformation ◽  
15Th Century ◽  
The Future ◽  
Secular Power

In the XIV century. centripetal tendencies began to appear in the Moscow principality. Inside the Russian church, several areas were distinguished. Part of the clergy supported the specificobar form. The other understood the need for transformations in society. As a result, this led to a split in the Russian church in the 15th century for "non-possessors" and "Josephites". The former linked the fate of the future with the ideology of hesychasm and its moral transformation, while the latter sought support in alliance with a strong secular power.

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