Anti-Myelin Oligodendrocyte Glycoprotein Encephalomyelitis and Extensive Longitudinal Transverse Myelitis Associated with Compound Heterozygous NLRP3 Missense Mutations in a Young Child

Compound Heterozygous ◽

Missense Mutations ◽

Childhood Onset

AbstractAcute disseminated encephalomyelitis in association with extensive longitudinal transverse myelitis is reported in a young child with positive anti-myelin oligodendrocyte glycoprotein (MOG) antibody with heterozygous NLRP3 missense mutations; p.(Arg488Lys) and p.(Ser159Ile). This case may well present an exceptional coincidence, but may describe a yet unrecognized feature of the spectrum of childhood onset cryopyrinopathies that contribute to the understanding of the genetic basis for anti-MOG antibody positive encephalomyelitis. Based on this observation, a larger scale study investigating the role of NLRP3 and other inflammasomes in this entity would provide important pathophysiological insights and potentially novel avenues for treatment.

Role of MRI evaluation in acute secondary inability to walk in children

Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1186/s43055-021-00417-0 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

K. H. Sedeek ◽

K. Aboualfotouh ◽

S. M. Hassanein ◽

N. M. Osman ◽

M. H. Shalaby

Keyword(s):

Transverse Myelitis ◽

High Sensitivity ◽

Limb Weakness ◽

Non Invasive ◽

Highly Sensitive ◽

Common Causes ◽

Bilateral Lower Limb ◽

Severity Of The Disease

Abstract Background Acute bilateral lower limb weakness is a common problem in children which necessitates a rapid method for diagnosis. MRI is a non-invasive imaging technique that produces high-quality images of the internal structure of the brain and spinal cord. Results MRI was very helpful in reaching rapid and prompt diagnosis in children with acute inability to walk. Acute disseminated encephalomyelitis (ADEM), Guillain–Barré syndrome (GBS), and acute transverse myelitis (ATM) were the most common causes in our study. MRI proved to be of high sensitivity in detecting the lesions and reaching the diagnosis in ADEM and GBS; however, there was no significant relation between the lesions’ size, enhancement pattern, and severity of the disease or prognosis, yet in ATM the site of the lesion and number of cord segment affection were significantly related to the severity of the disease and prognosis. Conclusion MRI is a quick tool to reach the diagnosis of children with acute secondary inability to walk, and to eliminate other differential diagnosis which is essential for proper treatment and rapid full recovery. It is highly sensitive in detecting the lesions, their site and size.

Case Report: Postvaccination Anti–Myelin Oligodendrocyte Glycoprotein Neuromyelitis Optica Spectrum Disorder

International Journal of MS Care ◽

10.7224/1537-2073.2018-104 ◽

2020 ◽

Vol 22 (2) ◽

pp. 85-90 ◽

Cited By ~ 1

Author(s):

Neha Kumar ◽

Kelsey Graven ◽

Nancy I. Joseph ◽

John Johnson ◽

Scott Fulton ◽

...

Keyword(s):

Neuromyelitis Optica ◽

Transverse Myelitis ◽

First Trimester ◽

Spectrum Disorder ◽

Aquaporin 4 ◽

Future Research ◽

Neuromyelitis Optica Spectrum Disorder ◽

The Central Nervous System

Abstract Stimulation of the immune response after vaccination can occasionally result in adverse effects, including demyelination of the central nervous system. The most common presentation of postvaccination demyelination is acute disseminated encephalomyelitis, but cases of optic neuritis, transverse myelitis, and multiple sclerosis relapses have been reported. More recently, an increasing number of postvaccination neuromyelitis optica spectrum disorder (NMOSD) cases have surfaced in the literature, especially in patients with aquaporin-4 antibodies. In this article, we report an unusual case of myelin oligodendrocyte glycoprotein antibody–related NMOSD after the receipt of multiple vaccines in a first-trimester pregnant woman from Africa. We review the reported cases of postvaccination demyelination in the past decade, with a focus on the relationship between NMOSD and vaccination in patients with aquaporin-4 or myelin oligodendrocyte glycoprotein antibodies. Finally, we discuss the clinical relevance of the present case and similar reported cases as it relates to patient care in the neuroimmunology clinic and identify potential areas for future research.

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

Pediatric anti-myelin oligodendrocyte glycoprotein syndrome: case series of a newly recognized central nervous system inflammatory disease

10.1017/cjn.2015.91 ◽

2015 ◽

Vol 42 (S1) ◽

pp. S15-S15

Author(s):

S Venkateswaran ◽

S Thulasirajah ◽

D Pohl ◽

K Rostasy

Keyword(s):

Case Series ◽

Transverse Myelitis ◽

Subcortical White Matter ◽

Imaging Features ◽

Initial Attack ◽

Inflammatory Conditions ◽

Inflammatory Brain Disease ◽

Extensive Involvement

Pediatric acquired demyelinating syndromes have overlapping clinical and imaging features, but management and prognosis vary. We describe four children between the ages of 3 and 10 presenting with inflammatory brain disease - one with polyfocal neurological symptoms, one with severe bilateral optic neuritis and two with transverse myelitis, all without encephalopathy. All brain MRIs had extensive involvement of both deep grey and subcortical white matter. Three patients had longitudinally extensive spinal cord lesions. Clinical and radiological findings did not meet criteria for multiple sclerosis, acute disseminated encephalomyelitis, or neuromyelitis optica (NMO). NMO IgG testing was negative. All patients had resolution of clinical and imaging findings after treatment with steroids and IVIg. We found, elevated levels of anti-myelin oligodendrocyte glycoprotein antibodies in all four patients. Three of the children receive monthly IVIg infusions. Two of the patients relapsed once within 18 months of their initial attack and have since remained relapse free for 32 months and 43 months, respectively. The third patient (transverse myelitis) has not had any relapses since her initial attack 15 months ago. It appears that children with this syndrome may have more favourable outcomes when compared to other CNS relapsing inflammatory conditions.

Relapsing optic neuritis and isolated transverse myelitis are the predominant clinical phenotypes for patients with antibodies to myelin oligodendrocyte glycoprotein in India

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217316675634 ◽

2016 ◽

Vol 2 ◽

pp. 205521731667563 ◽

Cited By ~ 8

Author(s):

Lekha Pandit ◽

Douglas Kazutoshi Sato ◽

Sharik Mustafa ◽

Toshiyuki Takahashi ◽

Anitha D’Cunha ◽

...

Keyword(s):

Optic Neuritis ◽

Transverse Myelitis ◽

Longitudinally Extensive Transverse Myelitis ◽

Clinical Phenotypes ◽

A Cell ◽

Demyelinating Disorders ◽

Aquaporin 4 Antibody ◽

Extensive Transverse Myelitis

Background Clinical phenotypes of patients with antibodies to myelin oligodendrocyte glycoprotein (anti-MOG+) are unknown in India. Objectives Retrospectively to characterise anti-MOG+ patients with inflammatory central nervous system disorders in India. Method A total of 87 patients with non-multiple sclerosis demyelinating disorders (excluding acute disseminated encephalomyelitis) who were seronegative for anti-aquaporin 4 antibody were retrospectively analysed using a cell-based assay for anti-MOG+ status. Results Twenty-five patients were anti-MOG+ in this cohort. They represented 28.7% (25/87) of patients who tested negative for anti-AQP4+. Sixty-four per cent (16/25) of anti-MOG+ patients were men and had a relapsing course. Patients with recurrent optic neuritis and those with a single attack of acute longitudinally extensive transverse myelitis were the most common phenotypes. Conclusion Relapsing optic neuritis was the most common phenotype, contrasting with a lower risk of relapses in transverse myelitis.

MOG Spectrum Disorders and Role of MOG-Antibodies in Clinical Practice

Neuropediatrics ◽

10.1055/s-0037-1604404 ◽

2017 ◽

Vol 49 (01) ◽

pp. 003-011 ◽

Cited By ~ 26

Author(s):

Eva-Maria Hennes ◽

Matthias Baumann ◽

Christian Lechner ◽

Kevin Rostásy

Keyword(s):

Transverse Myelitis ◽

Demyelinating Diseases ◽

Disease Course ◽

Older Children ◽

Radiological Features ◽

Age Dependent ◽

Mog Antibodies ◽

Spectrum Disorders

AbstractMyelin oligodendrocyte glycoprotein (MOG) antibodies (abs) are present in one third of all children with an acute demyelinating syndrome (ADS). MOG-abs can be found in acute disseminated encephalomyelitis (ADEM), transverse myelitis, isolated optic neuritis (ON), or recurrent demyelinating diseases, such as multiphasic neuromyelitis optica spectrum disorders (NMOSD) without aquaporin-4 (AQP4) abs or multiphasic ADEM (MDEM), but rarely in children who subsequently develop multiple sclerosis (MS). The presence of MOG-abs is age dependent with the highest seropositivity rates found in young children and an episode of ADEM, whereas older children with MOG-abs present with ON, myelitis, or brainstem symptoms. MOG-abs, initially thought to be associated with a benign disease course, are found in a substantial proportion of children with relapsing episodes associated with high and persisting MOG-ab titers. This review describes, in particular, the increasing spectrum of phenotypes associated with MOG-abs with a focus on clinical characteristics, radiological features, and therapeutic aspects.

Mutated p53 in HGSC—From a Common Mutation to a Target for Therapy

Cancers ◽

10.3390/cancers13143465 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3465

Author(s):

Aya Saleh ◽

Ruth Perets

Keyword(s):

Cancer Progression ◽

Target Genes ◽

P53 Protein ◽

Genetic Alterations ◽

Common Mutation ◽

Missense Mutations ◽

P53 Expression ◽

Histologic Subtype ◽

Tp53 Mutations

Mutations in tumor suppressor gene TP53, encoding for the p53 protein, are the most ubiquitous genetic variation in human ovarian HGSC, the most prevalent and lethal histologic subtype of epithelial ovarian cancer (EOC). The majority of TP53 mutations are missense mutations, leading to loss of tumor suppressive function of p53 and gain of new oncogenic functions. This review presents the clinical relevance of TP53 mutations in HGSC, elaborating on several recently identified upstream regulators of mutant p53 that control its expression and downstream target genes that mediate its roles in the disease. TP53 mutations are the earliest genetic alterations during HGSC pathogenesis, and we summarize current information related to p53 function in the pathogenesis of HGSC. The role of p53 is cell autonomous, and in the interaction between cancer cells and its microenvironment. We discuss the reduction in p53 expression levels in tumor associated fibroblasts that promotes cancer progression, and the role of mutated p53 in the interaction between the tumor and its microenvironment. Lastly, we discuss the potential of TP53 mutations to serve as diagnostic biomarkers and detail some more advanced efforts to use mutated p53 as a therapeutic target in HGSC.

Epistasis for Three Grain Yield Components in Rice (Oryxa sativa L.)

Genetics ◽

10.1093/genetics/145.2.453 ◽

1997 ◽

Vol 145 (2) ◽

pp. 453-465 ◽

Cited By ~ 6

Author(s):

Zhikang Li ◽

Shannon R M Pinson ◽

William D Park ◽

Andrew H Paterson ◽

James W Stansel

Keyword(s):

Grain Yield ◽

Complex Traits ◽

Yield Components ◽

Genetic Basis ◽

Kernel Weight ◽

Progeny Testing ◽

Grain Yield Components ◽

Main Effects ◽

Grain Number Per Panicle

The genetic basis for three grain yield components of rice, 1000 kernel weight (KW), grain number per panicle (GN), and grain weight per panicle (GWP), was investigated using restriction fragment length polymorphism markers and F4 progeny testing from a cross between rice subspecies japonica (cultivar Lemont from USA) and indica (cv. Teqing from China). Following identification of 19 QTL affecting these traits, we investigated the role of epistasis in genetic control of these phenotypes. Among 63 markers distributed throughout the genome that appeared to be involved in 79 highly significant (P < 0.001) interactions, most (46 or 73%) did not appear to have “main” effects on the relevant traits, but influenced the trait(s) predominantly through interactions. These results indicate that epistasis is an important genetic basis for complex traits such as yield components, especially traits of low heritability such as GN and GWP. The identification of epistatic loci is an important step toward resolution of discrepancies between quantitative trait loci mapping and classical genetic dogma, contributes to better understanding of the persistence of quantitative genetic variation in populations, and impels reconsideration of optimal mapping methodology and marker-assisted breeding strategies for improvement of complex traits.

Prediction of Functional Consequences of Missense Mutations in ANO4 Gene

International Journal of Molecular Sciences ◽

10.3390/ijms22052732 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2732

Author(s):

Nadine Reichhart ◽

Vladimir M. Milenkovic ◽

Christian H. Wetzel ◽

Olaf Strauß

Keyword(s):

Transmembrane Protein ◽

Functional Characterization ◽

Missense Mutations ◽

Mutant Proteins ◽

Functional Consequences ◽

New Perspective ◽

The Stability ◽

Dynamics Simulations ◽

And Function

The anoctamin (TMEM16) family of transmembrane protein consists of ten members in vertebrates, which act as Ca2+-dependent ion channels and/or Ca2+-dependent scramblases. ANO4 which is primarily expressed in the CNS and certain endocrine glands, has been associated with various neuronal disorders. Therefore, we focused our study on prioritizing missense mutations that are assumed to alter the structure and stability of ANO4 protein. We employed a wide array of evolution and structure based in silico prediction methods to identify potentially deleterious missense mutations in the ANO4 gene. Identified pathogenic mutations were then mapped to the modeled human ANO4 structure and the effects of missense mutations were studied on the atomic level using molecular dynamics simulations. Our data show that the G80A and A500T mutations significantly alter the stability of the mutant proteins, thus providing new perspective on the role of missense mutations in ANO4 gene. Results obtained in this study may help to identify disease associated mutations which affect ANO4 protein structure and function and might facilitate future functional characterization of ANO4.

Prevalence of ACSL (rs6552828) polymorphism among runners

Acta Kinesiologiae Universitatis Tartuensis ◽

10.12697/akut.2018.24.09 ◽

2019 ◽

Vol 24 ◽

pp. 121-128

Author(s):

Sigal Ben-Zaken ◽

Yoav Meckel ◽

Dan Nemet ◽

Alon Eliakim

Keyword(s):

Single Nucleotide Polymorphism ◽

Genetic Basis ◽

Maximal Oxygen Consumption ◽

Professional Athletes ◽

Distance Runners ◽

Nucleotide Polymorphism ◽

Long Distance ◽

Single Nucleotide ◽

The Common

The ACSL A/G polymorphism is associated with endurance trainability. Previous studies have demonstrated that homozygotes of the minor AA allele had a reduced maximal oxygen consumption response to training compared to the common GG allele homozygotes, and that the ACSL A/G single nucleotide polymorphism explained 6.1% of the variance in the VO2max response to endurance training. The contribution of ACSL single nucleotide polymorphism to endurance trainability was shown in nonathletes, however, its potential role in professional athletes is not clear. Moreover, the genetic basis to anaerobic trainability is even less studied. Therefore, the aim of the present study was to examine the prevalence of ACSL single nucleotide polymorphism among professional Israeli long distance runners (n=59), middle distance runners (n=31), sprinters and jumpers (n=48) and non-athletic controls (n=60). The main finding of the present study was that the ACSL1 AA genotype, previously shown to be associated with reduced endurance trainability, was not higher among sprinters and jumpers (15%) compared to middle- (16%) and long-distance runners (15%). This suggests that in contrast to previous studies indicating that the ACSL1 single nucleotide polymorphism may influence endurance trainability among non-athletic individuals, the role of this polymorphism among professional athletes is still not clear.

First Presentation of an Acquired Demyelinating Syndrome

Journal of Pediatric Neurology ◽

10.1055/s-0037-1606380 ◽

2017 ◽

Vol 16 (03) ◽

pp. 164-170

Author(s):

Rachel Gottlieb-Smith ◽

Amy Waldman

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Differential Diagnosis ◽

Optic Neuritis ◽

Clinical Features ◽

Neuromyelitis Optica ◽

Transverse Myelitis ◽

The Central Nervous System

AbstractAcquired demyelinating syndromes (ADS) present with acute or subacute monofocal or polyfocal neurologic deficits localizing to the central nervous system. The clinical features of distinct ADS have been carefully characterized including optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis. These disorders may all be monophasic disorders. Alternatively, optic neuritis, partial transverse myelitis, and acute disseminated encephalomyelitis may be first presentations of a relapsing or polyphasic neuroinflammatory disorder, such as multiple sclerosis or neuromyelitis optica. The clinical features of these disorders and the differential diagnosis are discussed in this article.