scholarly journals Clinics and genetic background of hereditary gingival fibromatosis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Karolina Strzelec ◽  
Agata Dziedzic ◽  
Katarzyna Łazarz-Bartyzel ◽  
Aleksander M. Grabiec ◽  
Ewa Gutmajster ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Rare Condition ◽  
Enrichment Score ◽  
Chromosome 2 ◽  
Chromosome 11 ◽  
Genetic Studies ◽  
Pathogenic Variants ◽  
Gingival Fibromatosis ◽  
Encoding Genes ◽  
Clinical Overview

Abstract Background Hereditary gingival fibromatosis (HGF) is a rare condition characterized by slowly progressive overgrowth of the gingiva. The severity of overgrowth may differ from mild causing phonetic and masticatory issues, to severe resulting in diastemas or malposition of teeth. Both, autosomal-dominant and autosomal-recessive forms of HGF are described. The aim of this review is a clinical overview, as well as a summary and discussion of the involvement of candidate chromosomal regions, pathogenic variants of genes, and candidate genes in the pathogenesis of HGF. The loci related to non-syndromic HGF have been identified on chromosome 2 (GINGF, GINGF3), chromosome 5 (GINGF2), chromosome 11 (GINGF4), and 4 (GINGF5). Of these loci, pathogenic variants of the SOS-1 and REST genes inducing HGF have been identified in the GINGF and the GINGF5, respectively. Furthermore, among the top 10 clusters of genes ranked by enrichment score, ATP binding, and fibronectin encoding genes were proposed as related to HGF. Conclusion The analysis of clinical reports as well as translational genetic studies published since the late’90s indicate the clinical and genetic heterogeneity of non-syndromic HGF and point out the importance of genetic studies and bioinformatics of more numerous unrelated families to identify novel pathogenic variants potentially inducing HGF. This strategy will help to unravel the molecular  mechanisms as well as uncover specific targets for novel and less invasive therapies of this rare, orphan condition.

Lighting a path: genetic studies pinpoint neurodevelopmental mechanisms in autism and related disorders

2012 ◽  
Vol 14 (3) ◽  
pp. 239-252
Keyword(s):  
Molecular Mechanisms ◽  
Protein Localization ◽  
Regulation Of Gene Expression ◽  
Neuronal Cell ◽  
Mrna Splicing ◽  
Genetic Mutations ◽  
Scaffolding Proteins ◽  
Molecular Processes ◽  
Genetic Studies ◽  
Novel Treatments

In this review, we outline critical molecular processes that have been implicated by discovery of genetic mutations in autism. These mechanisms need to be mapped onto the neurodevelopment step(s) gone awry that may be associated with cause in autism. Molecular mechanisms include: (i) regulation of gene expression; (ii) pre-mRNA splicing; (iii) protein localization, translation, and turnover; (iv) synaptic transmission; (v) cell signaling; (vi) the functions of cytoskeletal and scaffolding proteins; and (vii) the function of neuronal cell adhesion molecules. While the molecular mechanisms appear broad, they may converge on only one of a few steps during neurodevelopment that perturbs the structure, function, and/or plasticity of neuronal circuitry. While there are many genetic mutations involved, novel treatments may need to target only one of few developmental mechanisms.

Investigating the resistance levels and mechanisms to penoxsulam and cyhalofop-butyl in barnyardgrass (Echinochloa crus-galli) from Ningxia province, China

Weed Science ◽  
2021 ◽  
pp. 1-25
Author(s):  
Qian Yang ◽  
Xia Yang ◽  
Zichang Zhang ◽  
Jieping Wang ◽  
Weiguo Fu ◽  
...  
Keyword(s):  
Herbicide Resistance ◽  
Molecular Mechanisms ◽  
Acetolactate Synthase ◽  
Rice Fields ◽  
Target Site ◽  
Herbicide Resistant ◽  
Susceptible Populations ◽  
High Level ◽  
Als Inhibitor ◽  
Encoding Genes

Abstract Barnyardgrass (Echinochloa crus-galli) is a noxious grass weed which infests rice fields and causes huge crop yield losses. In this study, we collected twelve E. crus-galli populations from rice fields of Ningxia province in China and investigated the resistance levels to acetolactate synthase (ALS) inhibitor penoxsulam and acetyl-CoA carboxylase (ACCase) inhibitor cyhalofop-butyl. The results showed that eight populations exhibited resistance to penoxsulam and four populations evolved resistance to cyhalofop-butyl. Moreover, all of the four cyhalofop-butyl-resistant populations (NX3, NX4, NX6 and NX7) displayed multiple-herbicide-resistance (MHR) to both penoxsulam and cyhalofop-butyl. The alternative herbicides bispyribac-sodium, metamifop and fenoxaprop-P-ethyl cannot effectively control the MHR plants. To characterize the molecular mechanisms of resistance, we amplified and sequenced the target-site encoding genes in resistant and susceptible populations. Partial sequences of three ALS genes and six ACCase genes were examined. A Trp-574-Leu mutation was detected in EcALS1 and EcALS3 in two high-level (65.84- and 59.30-fold) penoxsulam-resistant populations NX2 and NX10, respectively. In addition, one copy (EcACC4) of ACCase genes encodes a truncated aberrant protein due to a frameshift mutation in E. crus-galli populations. None of amino acid substitutions that are known to confer herbicide resistance were detected in ALS and ACCase genes of MHR populations. Our study reveals the widespread of multiple-herbicide resistant E. crus-galli populations at Ningxia province of China that exhibit resistance to several ALS and ACCase inhibitors. Non-target-site based mechanisms are likely to be involved in E. crus-galli resistance to the herbicides, at least in four MHR populations.

scholarly journals Cellular and Molecular Mechanisms of Kidney Injury in 2,8-Dihydroxyadenine Nephropathy

2020 ◽  
Vol 31 (4) ◽  
pp. 799-816 ◽  
Author(s):  
Barbara Mara Klinkhammer ◽  
Sonja Djudjaj ◽  
Uta Kunter ◽  
Runolfur Palsson ◽  
Vidar Orn Edvardsson ◽  
...  
Keyword(s):  
Clinical Relevance ◽  
Molecular Mechanisms ◽  
Granulomatous Inflammation ◽  
Kidney Injury ◽  
Rare Condition ◽  
Therapeutic Interventions ◽  
Renal Tubules ◽  
Rodent Models ◽  
Adenine Phosphoribosyltransferase ◽  
Reparative Process

BackgroundHereditary deficiency of adenine phosphoribosyltransferase causes 2,8-dihydroxyadenine (2,8-DHA) nephropathy, a rare condition characterized by formation of 2,8-DHA crystals within renal tubules. Clinical relevance of rodent models of 2,8-DHA crystal nephropathy induced by excessive adenine intake is unknown.MethodsUsing animal models and patient kidney biopsies, we assessed the pathogenic sequelae of 2,8-DHA crystal-induced kidney damage. We also used knockout mice to investigate the role of TNF receptors 1 and 2 (TNFR1 and TNFR2), CD44, or alpha2-HS glycoprotein (AHSG), all of which are involved in the pathogenesis of other types of crystal-induced nephropathies.ResultsAdenine-enriched diet in mice induced 2,8-DHA nephropathy, leading to progressive kidney disease, characterized by crystal deposits, tubular injury, inflammation, and fibrosis. Kidney injury depended on crystal size. The smallest crystals were endocytosed by tubular epithelial cells. Crystals of variable size were excreted in urine. Large crystals obstructed whole tubules. Medium-sized crystals induced a particular reparative process that we term extratubulation. In this process, tubular cells, in coordination with macrophages, overgrew and translocated crystals into the interstitium, restoring the tubular luminal patency; this was followed by degradation of interstitial crystals by granulomatous inflammation. Patients with adenine phosphoribosyltransferase deficiency showed similar histopathological findings regarding crystal morphology, crystal clearance, and renal injury. In mice, deletion of Tnfr1 significantly reduced tubular CD44 and annexin two expression, as well as inflammation, thereby ameliorating the disease course. In contrast, genetic deletion of Tnfr2, Cd44, or Ahsg had no effect on the manifestations of 2,8-DHA nephropathy.ConclusionsRodent models of the cellular and molecular mechanisms of 2,8-DHA nephropathy and crystal clearance have clinical relevance and offer insight into potential future targets for therapeutic interventions.

scholarly journals Yield of peripheral sodium channels gene screening in pure small fibre neuropathy

2018 ◽  
Vol 90 (3) ◽  
pp. 342-352 ◽  
Author(s):  
Ivo Eijkenboom ◽  
Maurice Sopacua ◽  
Janneke G J Hoeijmakers ◽  
Bianca T A de Greef ◽  
Patrick Lindsey ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Clinical Features ◽  
Genetic Screening ◽  
Clinical Genetic ◽  
Genetic Studies ◽  
Small Fibre Neuropathy ◽  
Reference Centre ◽  
Pathogenic Variants ◽  
Small Fibre ◽  
Genetic Science

BackgroundNeuropathic pain is common in peripheral neuropathy. Recent genetic studies have linked pathogenic voltage-gated sodium channel (VGSC) variants to human pain disorders. Our aims are to determine the frequency of SCN9A, SCN10A and SCN11A variants in patients with pure small fibre neuropathy (SFN), analyse their clinical features and provide a rationale for genetic screening.MethodsBetween September 2009 and January 2017, 1139 patients diagnosed with pure SFN at our reference centre were screened for SCN9A, SCN10A and SCN11A variants. Pathogenicity of variants was classified according to established guidelines of the Association for Clinical Genetic Science and frequencies were determined. Patients with SFN were grouped according to the VGSC variants detected, and clinical features were compared.ResultsAmong 1139 patients with SFN, 132 (11.6%) patients harboured 73 different (potentially) pathogenic VGSC variants, of which 50 were novel and 22 were found in ≥ 1 patient. The frequency of (potentially) pathogenic variants was 5.1% (n=58/1139) for SCN9A, 3.7% (n=42/1139) for SCN10A and 2.9% (n=33/1139) for SCN11A. Only erythromelalgia-like symptoms and warmth-induced pain were significantly more common in patients harbouring VGSC variants.Conclusion(Potentially) pathogenic VGSC variants are present in 11.6% of patients with pure SFN. Therefore, genetic screening of SCN9A, SCN10A and SCN11A should be considered in patients with pure SFN, independently of clinical features or underlying conditions.

EEG1, a putative transporter expressed during epithelial organogenesis: comparison with embryonic transporter expression during nephrogenesis

2001 ◽  
Vol 281 (6) ◽  
pp. F1148-F1156 ◽  
Author(s):  
Robert O. Stuart ◽  
Anna Pavlova ◽  
David Beier ◽  
Zhixing Li ◽  
Yelena Krijanovski ◽  
...  
Keyword(s):  
Kidney Development ◽  
Fetal Liver ◽  
Organic Anion ◽  
Transport Proteins ◽  
Chromosome 2 ◽  
Dna Arrays ◽  
Chromosome 11 ◽  
New Family ◽  
Mouse Chromosome 2 ◽  
Eosinophil Major Basic Protein

A screen for genes differentially regulated in a model of kidney development identified the novel gene embryonic epithelia gene 1 (EEG1). EEG1 exists as two transcripts of 2.4 and 3.5 kb that are most highly expressed at embryonic day 7 and later in the fetal liver, lung, placenta, and kidney. The EEG1 gene is composed of 14 exons spanning a 20-kb region at human chromosome 11p12 and the syntenic region of mouse chromosome 2. Six EEG1 exons have previously been assigned to a longer isoform of eosinophil major basic protein termed proteoglycan 2. Another gene distantly related to EEG1, POV1/PB39, is located 88 kb upstream from the EEG1 gene on chromosome 11. Temporal expression of 65 members of the solute carrier (SLC)-class of transport proteins was followed during kidney development using DNA arrays. POV-1 and EEG1, like glucose transporters, displayed very early maximal gene expression. In contrast, other SLC genes, such as organic anion and cation transporters, amino acid permeases, and nucleoside transporters, had maximal expression later in development. Thus, although the bulk of transporters are expressed late in kidney development, a fraction are expressed near the onset of nephrogenesis. The data raise the possibility that EEG1 and POV1 may define a new family of transport proteins involved in the transport of nutrients or metabolites in rapidly growing and/or developing tissues.

scholarly journals A Yeast-Based Model for Hereditary Motor and Sensory Neuropathies: A Simple System for Complex, Heterogeneous Diseases

2020 ◽  
Vol 21 (12) ◽  
pp. 4277 ◽  
Author(s):  
Weronika Rzepnikowska ◽  
Joanna Kaminska ◽  
Dagmara Kabzińska ◽  
Katarzyna Binięda ◽  
Andrzej Kochański
Keyword(s):  
Molecular Mechanisms ◽  
Genetic Diagnosis ◽  
Clinical Manifestations ◽  
Model System ◽  
Research Field ◽  
Therapeutic Approaches ◽  
Rare Disorders ◽  
Advantages And Disadvantages ◽  
Pathogenic Variants ◽  
Disease Subtypes

Charcot–Marie–Tooth (CMT) disease encompasses a group of rare disorders that are characterized by similar clinical manifestations and a high genetic heterogeneity. Such excessive diversity presents many problems. Firstly, it makes a proper genetic diagnosis much more difficult and, even when using the most advanced tools, does not guarantee that the cause of the disease will be revealed. Secondly, the molecular mechanisms underlying the observed symptoms are extremely diverse and are probably different for most of the disease subtypes. Finally, there is no possibility of finding one efficient cure for all, or even the majority of CMT diseases. Every subtype of CMT needs an individual approach backed up by its own research field. Thus, it is little surprise that our knowledge of CMT disease as a whole is selective and therapeutic approaches are limited. There is an urgent need to develop new CMT models to fill the gaps. In this review, we discuss the advantages and disadvantages of yeast as a model system in which to study CMT diseases. We show how this single-cell organism may be used to discriminate between pathogenic variants, to uncover the mechanism of pathogenesis, and to discover new therapies for CMT disease.

scholarly journals Revealing the role of phospholipase Cβ3 in the regulation of VEGF-induced vascular permeability

Blood ◽  
2012 ◽  
Vol 120 (11) ◽  
pp. 2167-2173 ◽  
Author(s):  
Luke H. Hoeppner ◽  
Kathryn N. Phoenix ◽  
Karl J. Clark ◽  
Resham Bhattacharya ◽  
Xun Gong ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Real Time ◽  
Molecular Mechanisms ◽  
Negative Regulator ◽  
Transgenic Zebrafish ◽  
Genetic Studies ◽  
In Vivo Models ◽  
Ischemic Diseases

AbstractVEGF induces vascular permeability (VP) in ischemic diseases and cancer, leading to many pathophysiological consequences. The molecular mechanisms by which VEGF acts to induce hyperpermeability are poorly understood and in vivo models that easily facilitate real-time, genetic studies of VP do not exist. In the present study, we report a heat-inducible VEGF transgenic zebrafish (Danio rerio) model through which VP can be monitored in real time. Using this approach with morpholino-mediated gene knock-down and knockout mice, we describe a novel role of phospholipase Cβ3 as a negative regulator of VEGF-mediated VP by regulating intracellular Ca2+ release. Our results suggest an important effect of PLCβ3 on VP and provide a new model with which to identify genetic regulators of VP crucial to several disease processes.

scholarly journals Chitayat-Hall and Schaaf-Yang syndromes:a common aetiology: expanding the phenotype of MAGEL2-related disorders

2018 ◽  
Vol 55 (5) ◽  
pp. 316-321 ◽  
Author(s):  
Rebekah Jobling ◽  
Dimitri James Stavropoulos ◽  
Christian R Marshall ◽  
Cheryl Cytrynbaum ◽  
Michelle M Axford ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Clinical Manifestations ◽  
Rare Condition ◽  
Hormone Deficiency ◽  
Truncated Protein ◽  
Dysmorphic Features ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
And Inversion

BackgroundChitayat-Hall syndrome, initially described in 1990, is a rare condition characterised by distal arthrogryposis, intellectual disability, dysmorphic features and hypopituitarism, in particular growth hormone deficiency. The genetic aetiology has not been identified.Methods and resultsWe identified three unrelated families with a total of six affected patients with the clinical manifestations of Chitayat-Hall syndrome. Through whole exome or whole genome sequencing, pathogenic variants in the MAGEL2 gene were identified in all affected patients. All disease-causing sequence variants detected are predicted to result in a truncated protein, including one complex variant that comprised a deletion and inversion.ConclusionsChitayat-Hall syndrome is caused by pathogenic variants in MAGEL2 and shares a common aetiology with the recently described Schaaf-Yang syndrome. The phenotype of MAGEL2-related disorders is expanded to include growth hormone deficiency as an important and treatable complication.

scholarly journals Rare case report of idiopathic gingival fibromatosis in childhood and its management

2019 ◽  
Vol 12 (1) ◽  
pp. e227942
Author(s):  
Morankar Rahul ◽  
Krishan Gauba ◽  
Nitin Gorwade ◽  
Aman Kumar
Keyword(s):  
Age Of Onset ◽  
Rare Condition ◽  
Radiographic Examination ◽  
Oral Manifestations ◽  
Gingival Enlargement ◽  
Rare Case Report ◽  
Scalpel Blade ◽  
Gingival Fibromatosis ◽  
Mandibular Teeth ◽  
Almost All

Idiopathic gingival fibromatosis (GF), also known as gingivomatosis, is a rare condition in childhood, with an unknown aetiology. The oral manifestations of the condition are varied and depend on the severity and age of involvement. This paper describe the case of a 5-year-old male child with extensive gingival enlargement covering almost all the maxillary and mandibular teeth resulted in difficulty with speech, mastication and poor aesthetics. Clinical and radiographic examination along with haematological investigations ruled out any systemic association. The case was managed with conventional scalpel blade surgery along with electrocautery under general anaesthesia yielding good results without any recurrence after a 12-month follow-up. The results revealed that the oral manifestations of GF depend on its severity and the age of onset. Timely intervention can help to prevent associated complications in a growing child.

scholarly journals Transgenerational Inheritance of Environmentally Induced Epigenetic Alterations during Mammalian Development

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1559 ◽  
Author(s):  
Louis Legoff ◽  
Shereen Cynthia D’Cruz ◽  
Sergei Tevosian ◽  
Michael Primig ◽  
Fatima Smagulova
Keyword(s):  
Molecular Mechanisms ◽  
Disease Risk ◽  
Current Knowledge ◽  
Epigenetic Inheritance ◽  
Epigenetic Alterations ◽  
Transgenerational Inheritance ◽  
Mammalian Development ◽  
Genetic Studies ◽  
Salient Points ◽  
Chromatin Proteins

Genetic studies traditionally focus on DNA as the molecule that passes information on from parents to their offspring. Changes in the DNA code alter heritable information and can more or less severely affect the progeny’s phenotype. While the idea that information can be inherited between generations independently of the DNA’s nucleotide sequence is not new, the outcome of recent studies provides a mechanistic foundation for the concept. In this review, we attempt to summarize our current knowledge about the transgenerational inheritance of environmentally induced epigenetic changes. We focus primarily on studies using mice but refer to other species to illustrate salient points. Some studies support the notion that there is a somatic component within the phenomenon of epigenetic inheritance. However, here, we will mostly focus on gamete-based processes and the primary molecular mechanisms that are thought to contribute to epigenetic inheritance: DNA methylation, histone modifications, and non-coding RNAs. Most of the rodent studies published in the literature suggest that transgenerational epigenetic inheritance through gametes can be modulated by environmental factors. Modification and redistribution of chromatin proteins in gametes is one of the major routes for transmitting epigenetic information from parents to the offspring. Our recent studies provide additional specific cues for this concept and help better understand environmental exposure influences fitness and fidelity in the germline. In summary, environmental cues can induce parental alterations and affect the phenotypes of offspring through gametic epigenetic inheritance. Consequently, epigenetic factors and their heritability should be considered during disease risk assessment.

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