Abstract:
:Rett syndrome is a severe neurodevelopmental disorder, almost exclusively affecting females and characterized by a wide spectrum of clinical manifestations. Both the classic and atypical forms of Rett syndrome are primarily due to mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in patients with atypical Rett syndrome, X-linked infantile spasms sharing common features of generally early-onset seizures and mental retardation. CDKL5 is known as serine/threonine protein kinase 9 (STK9) and is mapped to the Xp22 region. It has a conserved serine/threonine kinase domain within its amino terminus and a large C-terminal region. Disease-causing mutations are distributed in both the amino terminal domain and in the large C-terminal domain. We have screened the CDKL5 gene in 44 patients with atypical Rett syndrome who had tested negative for MECP2 gene mutations and have identified 6 sequence variants, out of which three were novel and three known mutations. Two of these novel mutations p.V966I and p.A1011V were missense and p.H589H a silent mutation. Other known mutations identified were p.V999M, p.Q791P and p.T734A. Sequence homology for all the mutations revealed that the two mutations (p.Q791P and p.T734A) were conserved across species. This indicated the importance of these residues in structure and function of the protein. The damaging effects of these mutations were analysed in silico using PolyPhen-2 online software. The PolyPhen-2 scores of p.Q791P and p.T734A were 0.998 and 0.48, revealing that these mutations could be deleterious and might have potential functional effect. All other mutations had a low score suggesting that they might not alter the activity of CDKL5. We have also analysed the position of the mutations in the CDKL5 protein and found that all the mutations were present in the C-terminal domain of the protein. The C-terminal domain is required for cellular localization through protein-protein interaction; any mutations in this domain might alter this function of the protein. This is the first report from India showing the mutation in CDKL5 gene in Indian cases of Rett syndrome. Our study emphasizes the role of CDKL5 mutation screening in cases of atypical Rett syndrome with congenital seizure variant.
journal_name
Neuromolecular Medjournal_title
Neuromolecular medicineauthors
Das DK,Mehta B,Menon SR,Raha S,Udani Vdoi
10.1007/s12017-012-8212-zsubject
Has Abstractpub_date
2013-03-01 00:00:00pages
218-25issue
1eissn
1535-1084issn
1559-1174journal_volume
15pub_type
杂志文章abstract::Elevated C-reactive protein (CRP) levels increase the risk of poor functional disability in patients with ischemic stroke (IS). This study aimed to investigate the association between CRP gene polymorphisms and 3-month functional disability of large artery atherosclerotic (LAA) stroke in Han Chinese. Patients with fir...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-018-8485-y
更新日期:2018-06-01 00:00:00
abstract::Sphingosine 1-phosphates (S1Ps) are bioactive lipids that mediate a diverse range of effects through the activation of cognate receptors, S1P1-S1P5. Scrutiny of S1P-regulated pathways over the past three decades has identified important and occasionally counteracting functions in the brain and cerebrovascular system. ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-020-08632-0
更新日期:2020-11-12 00:00:00
abstract::Renalase is a novel, recently identified, flavin adenine dinucleotide-dependent amine oxidase. It is secreted by the kidney and metabolizes circulating catecholamines. Renalase has significant hemodynamic effects, therefore it is likely to participate in the regulation of cardiovascular function.The aim of our study w...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-011-8158-6
更新日期:2011-12-01 00:00:00
abstract::Autism spectrum disorder (ASD) is a heterogeneously childhood neurodevelopmental disorder, believed to be under development of various genetic and environmental factors. Autophagy and related pathways have also been implicated in the etiology of ASD. We aimed to investigate autophagic markers by generating the transge...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-019-08579-x
更新日期:2020-06-01 00:00:00
abstract::Functional electrical stimulation (FES) has been widely adopted to elicit muscle contraction in rehabilitation training after spinal cord injury (SCI). Conventional FES modalities include stimulations coupled with rowing, cycling, assisted walking and other derivatives. In this review, we studied thirteen clinical rep...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-019-08589-9
更新日期:2020-12-01 00:00:00
abstract::A number of studies have investigated the association between tumor necrosis factor (TNF)-α gene polymorphisms and ischemic stroke susceptibility. However, results of different individual studies are often inconsistent. To provide a more robust evaluation of the association between polymorphisms of the TNF-α gene and ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s12017-015-8365-7
更新日期:2015-12-01 00:00:00
abstract::P-glycoprotein (P-gp), which is coded by the MDR1 gene, in the brain capillary endothelial cell limits the entry of many drugs including antipsychotics into the brain. The aim of this study is to examine whether a functional polymorphism, a C to T substitution at position 3435 in exon 26 of the MDR1 gene, is associate...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-008-8041-2
更新日期:2008-01-01 00:00:00
abstract::Abnormal interactions and misfolding of synaptic proteins in the nervous system are being extensively explored as important pathogenic events resulting in neurodegeneration in various neurological disorders. These include Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy bodies (DLB). In AD, m...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1385/NMM:4:1-2:21
更新日期:2003-01-01 00:00:00
abstract::Adenosine A2A receptor (A2AR) is a G-protein-coupled receptor highly expressed in basal ganglia. Its expression levels are severely reduced in Huntington's disease (HD), and several pharmacological therapies have shown its implication in this neurodegenerative disorder. The main goal of this study was to gain insight ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-013-8219-0
更新日期:2013-06-01 00:00:00
abstract::The metabolic syndrome is characterized by the clustering of various common metabolic abnormalities in an individual and it is associated with increased risk for the development of type 2 diabetes and cardiovascular diseases. Its prevalence in the general population is approximately 25%. Central fat accumulation and i...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-008-8022-5
更新日期:2008-01-01 00:00:00
abstract::Millions of individuals with active TB do not receive recommended treatments, and instead may use botanicals, or use botanicals concurrently with established treatments. Many botanicals protect against oxidative stress, but this can interfere with redox-dependent activation of isoniazid and other prodrugs used for pro...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-016-8402-1
更新日期:2016-09-01 00:00:00
abstract::T-cells directed to self-antigens ("autoimmune" T-cells) have traditionally been perceived as tending to attack the body's own tissues, and likely to exert their destructive effects unless they undergo deletion in the thymus during ontogeny. Naturally occurring CD4+CD25+ regulatory T-cells were viewed as thymus-derive...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1385/NMM:7:3:197
更新日期:2005-01-01 00:00:00
abstract::Classically, histologic grading of gliomas has been used to predict seizure association, with low-grade gliomas associated with an increased incidence of seizures compared to high-grade gliomas. In 2016, WHO reclassified gliomas based on histology and molecular characteristics. We sought to determine whether molecular...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-020-08624-0
更新日期:2020-11-18 00:00:00
abstract::The present study demonstrates the efficacies of synthetic 1,8-cineole and an 1,8-cineole-rich supercritical carbon dioxide (SC-CO2) extract of small cardamom seeds in preventing oligomerization of amyloid beta peptide (Aβ42) and inhibiting iron-dependent oxyradical production in vitro. The oligomerization of Aβ42 was...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-019-08574-2
更新日期:2020-03-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily affects motor neurons and descending motor tracts of the CNS. We have evaluated the CNS of a murine model of familial ALS based on the over-expression of mutant human superoxide dismutase (mSOD; G93A) using magnetic resonance microscopy ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-007-8002-1
更新日期:2007-01-01 00:00:00
abstract::Phospholipids are the main constituents of brain membranes. Formation of new membranes requires that uridine, the omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA), and choline, the three circulating precursors of major phospholipids, interact via the Kennedy pathway. Supplementation of laboratory...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-016-8414-x
更新日期:2016-09-01 00:00:00
abstract::Astrocytes are principal mediators of homeostasis in the central nervous system (CNS). They supply neurons and oligodendrocytes with substrates for energy metabolism and clear the extracellular space of excess neurotransmitters. In neuroinflammation, astrocytes have classically been regarded as unimportant since their...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1385/nmm:9:1:1
更新日期:2007-01-01 00:00:00
abstract::Homocysteine (Hcy) is a sulfur-containing amino acid derived from methionine metabolism. Elevated plasma Hcy levels (> 15 µM) result in a condition called hyperhomocysteinemia (HHcy), which is an independent risk factor in the development of various neurodegenerative disorders. Reactive oxygen species (ROS) produced b...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-018-8505-y
更新日期:2018-12-01 00:00:00
abstract::Cyclin H regulates cell cycle transitions; it always forms trimeric cyclin-dependent protein kinases (CDK)-activating kinase (CAK) complex with CDK7 and MAT1 that phosphorylates a threonine residue in the CDK2 T loop region. However, neither the expression nor function of cyclin H in the central nervous system (CNS) i...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-011-8150-1
更新日期:2011-09-01 00:00:00
abstract::Attention deficit hyperactivity disorder (ADHD) is a behavioral diagnosis based on the presence of developmentally inappropriate levels of impulsivity, overactivity, and inattentiveness. It is a familial condition with a complex pattern of inheritance. Variation of several genes involved in the regulation of dopamine,...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1385/NMM:8:4:461
更新日期:2006-01-01 00:00:00
abstract::In addition to myelin loss and oligodendrocyte injury, axonal damage is a major cause of irreversible neurological disability in multiple sclerosis (MS). A series of studies have demonstrated that Rho kinase (ROCK) is involved in synaptic plasticity of neurons. Here, we found that ROCK activity in MS serum was elevate...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-015-8374-6
更新日期:2015-12-01 00:00:00
abstract::A major component of green tea, a widely consumed beverage, is (-)-epigallocatechin gallate (EGCG), which has strong antioxidant properties. Our previous study has indicated that free radical production following rat traumatic brain injury (TBI) induces neural degeneration. In this study, we investigated the effects o...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-011-8162-x
更新日期:2011-12-01 00:00:00
abstract::Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a genetic and early-onset neurodegenerative disorder characterized by iron accumulation in the basal ganglia. It is due to mutations in Pantothenate Kinase 2 (PANK2), an enzyme that catalyzes the phosphorylation of vitamin B5, first and essential step in coenz...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-018-8508-8
更新日期:2019-06-01 00:00:00
abstract::Familial dysautonomia (FD) is a sensory and autonomic neuropathy that affects the development and survival of sensory, sympathetic, and some parasympathetic neurons. It is autosomally inherited and occurs almost exclusively among individuals of Ashkenazi Jewish descent. The pathological and clinical manifestations of ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-007-8019-5
更新日期:2008-01-01 00:00:00
abstract::Substantial evidence indicates bioenergetic dysfunction and mitochondrial impairment contribute either directly and/or indirectly to the pathogenesis of numerous neurodegenerative disorders. Treatment paradigms aimed at ameliorating this cellular energy deficit and/or improving mitochondrial function in these neurodeg...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-008-8053-y
更新日期:2008-01-01 00:00:00
abstract::A methylation-based EWAS on carefully phenotyped individuals with Parkinson's disease (PD) was conducted to reveal prioritised genes and pathways with statistically significant and sizable changes in PD and in the anxiety that often accompanies it. This was followed by subsequent replication of top-ranked CpG sites. U...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-014-8332-8
更新日期:2014-12-01 00:00:00
abstract::Hemorrhagic transformation (HT) of cerebral infarction is a common and serious occurrence following acute ischemic stroke. The expression of survivin, a member of the inhibitor of apoptosis protein family, has been shown to increase after cerebral ischemia. This protein has been mainly located at the microvasculature ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-014-8333-7
更新日期:2014-12-01 00:00:00
abstract::Epidemiological studies demonstrate that pain frequently occurs comorbid with depression. Gentiopicroside (Gent) is a secoiridoid compound isolated from Gentiana lutea that exhibits analgesic properties and inhibits the expression of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the anterior cingulate cor...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-013-8280-8
更新日期:2014-06-01 00:00:00
abstract::The original version of this article unfortunately contained a mistake. Gary S. Laco should not be listed as an author in the author group. ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,已发布勘误
doi:10.1007/s12017-020-08593-4
更新日期:2020-06-01 00:00:00
abstract::Parkinson's disease (PD) is the most common neurodegenerative motor disorder, marked by chronic progressive loss of neurons in the substantia nigra, thereby damaging purposeful control of movement. For decades, it was believed that PD was caused solely by environmental causes. However, the discovery of genetic factors...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1385/NMM:1:2:95
更新日期:2002-01-01 00:00:00