The defective gene DYS, which is responsible for familial dysautonomia (FD) and has been mapped to a 0.5-cM region on chromosome 9q31, has eluded identification. We identified and characterized the RNAs encoded by this region of chromosome 9 in cell lines derived from individuals homozygous for the major FD haplotype, and we observed that the RNA encoding the IkappaB kinase complex-associated protein (IKAP) lacks exon 20 and, as a result of a frameshift, encodes a truncated protein. Sequence analysis reveals a T-->C transition in the donor splice site of intron 20. In individuals bearing a minor FD haplotype, a missense mutation in exon 19 disrupts a consensus serine/threonine kinase phosphorylation site. This mutation results in defective phosphorylation of IKAP. These mutations were observed to be present in a random sample of Ashkenazi Jewish individuals, at approximately the predicted carrier frequency of FD. These findings demonstrate that mutations in the gene encoding IKAP are responsible for FD.
Characterization of IKI1 and IKI3 genes conferring pGKL killer sensitivity on Saccharomyces cerevisiae
Elongator, a multisubunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation
Precise genetic mapping and haplotype analysis of the familial dysautonomia gene on human chromosome 9q31
Therapeutic potential and mechanism of kinetin as a treatment for the human splicing disease familial dysautonomia
Fludrocortisone in patients with familial dysautonomia--assessing effect on clinical parameters and gene expression
Screening of substrate peptide sequences for tissue-type transglutaminase (TGase 2) using T7 phage cDNA library
The molecular basis of familial dysautonomia: overview, new discoveries and implications for directed therapies
Of splice and men: what does the distribution of IKAP mRNA in the rat tell us about the pathogenesis of familial dysautonomia?
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tRNA tKUUU, tQUUG, and tEUUC wobble position modifications fine-tune protein translation by promoting ribosome A-site binding
4-Phenylbutyrate stimulates Hsp70 expression through the Elp2 component of elongator and STAT-3 in cystic fibrosis epithelial cells.
DERP6 (ELP5) and C3ORF75 (ELP6) regulate tumorigenicity and migration of melanoma cells as subunits of Elongator
Can the therapeutic efficacy of tocotrienols in neurodegenerative familial dysautonomia patients be measured clinically?
Hereditary sensory neuropathy is caused by a mutation in the delta subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct4 ) gene
Molecular screening for diseases frequent in Ashkenazi Jews: lessons learned from more than 100,000 tests performed in a commercial laboratory
Gastroesophageal reflux in familial dysautonomia: correlation with crisis frequency and sensory dysfunction
A founder mutation in the Ashkenazi Jewish population affecting messenger RNA splicing of the CCM2 gene causes cerebral cavernous malformations
Mutations in ABO1/ELO2, a subunit of holo-Elongator, increase abscisic acid sensitivity and drought tolerance in Arabidopsis thaliana
Loss of mouse Ikbkap, a subunit of elongator, leads to transcriptional deficits and embryonic lethality that can be rescued by human IKBKAP
Elongator subunit 3 positively regulates plant immunity through its histone acetyltransferase and radical S-adenosylmethionine domains
IKBKAP mRNA in peripheral blood leukocytes: a molecular marker of gene expression and splicing in familial dysautonomia
Kinetin in familial dysautonomia carriers: implications for a new therapeutic strategy targeting mRNA splicing
Defects in tRNA modification associated with neurological and developmental dysfunctions in Caenorhabditis elegans elongator mutants
Enriched population of PNS neurons derived from human embryonic stem cells as a platform for studying peripheral neuropathies
Olfactory stem cells, a new cellular model for studying molecular mechanisms underlying familial dysautonomia
Effects of IKAP/hELP1 deficiency on gene expression in differentiating neuroblastoma cells: implications for familial dysautonomia
Deletion of exon 20 of the Familial Dysautonomia gene Ikbkap in mice causes developmental delay, cardiovascular defects, and early embryonic lethality
IKAP/Elp1 is required in vivo for neurogenesis and neuronal survival, but not for neural crest migration
IKAP deficiency in an FD mouse model and in oligodendrocyte precursor cells results in downregulation of genes involved in oligodendrocyte differentiation and myelin formation
Genetic factors underlying the risk of bortezomib induced peripheral neuropathy in multiple myeloma patients
Familial dysautonomia model reveals Ikbkap deletion causes apoptosis of Pax3+ progenitors and peripheral neurons
Elongator is a histone H3 and H4 acetyltransferase important for normal histone acetylation levels in vivo
Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway
Axon Transport and Neuropathy: Relevant Perspectives on the Etiopathogenesis of Familial Dysautonomia
Deregulated expression of pro-survival and pro-apoptotic p53-dependent genes upon Elongator deficiency in colon cancer cells
Elongator mediates ABA responses, oxidative stress resistance and anthocyanin biosynthesis in Arabidopsis
Haploinsufficiency of the nerve growth factor beta gene in a 1p13 deleted female child with an insensitivity to pain
Cardiac glycosides correct aberrant splicing of IKBKAP-encoded mRNA in familial dysautonomia derived cells by suppressing expression of SRSF3
Genome-wide analysis of familial dysautonomia and kinetin target genes with patient olfactory ecto-mesenchymal stem cells
Nutraceutical-mediated restoration of wild-type levels of IKBKAP-encoded IKAP protein in familial dysautonomia-derived cells
A conserved and essential basic region mediates tRNA binding to the Elp1 subunit of the Saccharomyces cerevisiae Elongator complex
Arabidopsis Elongator subunit 2 positively contributes to resistance to the necrotrophic fungal pathogens Botrytis cinerea and Alternaria brassicicola
Defects in tRNA Anticodon Loop 2'-O-Methylation Are Implicated in Nonsyndromic X-Linked Intellectual Disability due to Mutations in FTSJ1
Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism
The bright side of JNKs-Multitalented mediators in neuronal sprouting, brain development and nerve fiber regeneration
Elongator-dependent modification of cytoplasmic tRNALysUUU is required for mitochondrial function under stress conditions
Elevated levels of two tRNA species bypass the requirement for elongator complex in transcription and exocytosis
Transcription impairment and cell migration defects in elongator-depleted cells: implication for familial dysautonomia
Elongator controls the migration and differentiation of cortical neurons through acetylation of alpha-tubulin
Familial dysautonomia (FD) patients have reduced levels of the modified wobble nucleoside mcm(5)s(2)U in tRNA
Tissue-specific reduction in splicing efficiency of IKBKAP due to the major mutation associated with familial dysautonomia
Identification of host cell proteins which interact with herpes simplex virus type 1 tegument protein pUL37
Conservation of an intricate circuit for crucial modifications of the tRNAPhe anticodon loop in eukaryotes
Tension-type headache as the unique pain experience of a patient with congenital insensitivity to pain
Heritability of nociception. III. Genetic relationships among commonly used assays of nociception and hypersensitivity
Involvement of IKAP in peripheral target innervation and in specific JNK and NGF signaling in developing PNS neurons
Phosphatidylserine Ameliorates Neurodegenerative Symptoms and Enhances Axonal Transport in a Mouse Model of Familial Dysautonomia
Proteasome inhibitors to alleviate aberrant IKBKAP mRNA splicing and low IKAP/hELP1 synthesis in familial dysautonomia
Silencing SlELP2L, a tomato Elongator complex protein 2-like gene, inhibits leaf growth, accelerates leaf, sepal senescence, and produces dark-green fruit
Neurotrophic support and oxidative stress: converging effects in the normal and diseased nervous system
Lack of 2'-O-methylation in the tRNA anticodon loop of two phylogenetically distant yeast species activates the general amino acid control pathway
Exon-specific U1 snRNAs improve ELP1 exon 20 definition and rescue ELP1 protein expression in a familial dysautonomia mouse model
MicroRNA screening identifies a link between NOVA1 expression and a low level of IKAP in familial dysautonomia
The familial dysautonomia disease gene IKBKAP is required in the developing and adult mouse central nervous system
Retina-specific loss of Ikbkap/Elp1 causes mitochondrial dysfunction that leads to selective retinal ganglion cell degeneration in a mouse model of familial dysautonomia
Familial insensitivity to pain (HSAN V) and a mutation in the NGFB gene. A neurophysiological and pathological study
Carrier frequency of autosomal-recessive disorders in the Ashkenazi Jewish population: should the rationale for mutation choice for screening be reevaluated?
Molecular architecture of the yeast Elongator complex reveals an unexpected asymmetric subunit arrangement
Exploratory analyses of consensus molecular subtype-dependent associations of TP53 mutations with immunomodulation and prognosis in colorectal cancer.
The pathogenicity of splicing defects: mechanistic insights into pre-mRNA processing inform novel therapeutic approaches
Familial dysautonomia: detection of the IKBKAP IVS20(+6T --> C) and R696P mutations and frequencies among Ashkenazi Jews
Case scenario: perioperative administration of tocotrienols and green tea extract in a child with familial dysautonomia
Blocking of an intronic splicing silencer completely rescues IKBKAP exon 20 splicing in familial dysautonomia patient cells
Involvement of BcElp4 in vegetative development, various environmental stress response and virulence of Botrytis cinerea
Antisense oligonucleotides correct the familial dysautonomia splicing defect in IKBKAP transgenic mice
Induced pluripotent stem cells for disease modeling, cell therapy and drug discovery in genetic autonomic disorders: a review
Von Economo Neuron Pathology in Familial Dysautonomia: Quantitative Assessment and Possible Implications.
Increasing cutaneous afferent feedback improves proprioceptive accuracy at the knee in patients with sensory ataxia
Integrated Computational Analysis of Genes Associated with Human Hereditary Insensitivity to Pain. A Drug Repurposing Perspective
Combinatorial treatment increases IKAP levels in human cells generated from Familial Dysautonomia patients
IKAP/hELP1 down-regulation in neuroblastoma cells causes enhanced cell adhesion mediated by contactin overexpression
RBM24 promotes U1 snRNP recognition of the mutated 5' splice site in the IKBKAP gene of familial dysautonomia
tRNA-Derived Small RNAs: Biogenesis, Modification, Function and Potential Impact on Human Disease Development
Identification of the enzymes responsible for m2,2G and acp3U formation on cytosolic tRNA from insects and plants
Retrograde nerve growth factor signaling abnormalities and the pathogenesis of familial dysautonomia.
Subcellular relocalization and nuclear redistribution of the RNA methyltransferases TRMT1 and TRMT1L upon neuronal activation.
IKAP localizes to membrane ruffles with filamin A and regulates actin cytoskeleton organization and cell migration
A neuron autonomous role for the familial dysautonomia gene ELP1 in sympathetic and sensory target tissue innervation
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