keyword
MENU ▼
Read by QxMD icon Read
search

Haploinsufficiency

keyword
https://www.readbyqxmd.com/read/27906774/lessons-from-characterization-and-treatment-of-the-autoinflammatory-syndromes
#1
Ivona Aksentijevich, Michael F McDermott
PURPOSE OF REVIEW: The list of genes associated with systemic inflammatory diseases has been steadily growing because of the explosion of new genomic technologies. Significant advances in the past year have deepened our understanding of the molecular mechanisms linked to inflammation and elucidated insights on the efficacy of specific therapies for these and related conditions. We review the molecular pathogenesis of four recently characterized monogenic autoinflammatory diseases: haploinsufficiency of A20, otulipenia, a severe form of pyrin-associated disease, and a monogenic form of systemic juvenile idiopathic arthritis...
November 30, 2016: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/27906108/heme-oxygenase-and-carbon-monoxide-protect-from-muscle-dystrophy
#2
Mun Chun Chan, Olivia Ziegler, Laura Liu, Glenn C Rowe, Saumya Das, Leo E Otterbein, Zoltan Arany
BACKGROUND: Duchenne muscle dystrophy (DMD) is one of the most common lethal genetic diseases of children worldwide and is 100% fatal. Steroids, the only therapy currently available, are marred by poor efficacy and a high side-effect profile. New therapeutic approaches are urgently needed. METHODS: Here, we leverage PGC-1α, a powerful transcriptional coactivator known to protect against dystrophy in the mdx murine model of DMD, to search for novel mechanisms of protection against dystrophy...
November 28, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905298/haploinsufficiency-of-the-folliculin-gene-leads-to-impaired-functions-of-lung-fibroblasts-in-patients-with-birt-hogg-dub%C3%A3-syndrome
#3
Yoshito Hoshika, Fumiyuki Takahashi, Shinsaku Togo, Muneaki Hashimoto, Takeshi Nara, Toshiyuki Kobayashi, Fariz Nurwidya, Hideyuki Kataoka, Masatoshi Kurihara, Etsuko Kobayashi, Hiroki Ebana, Mika Kikkawa, Katsutoshi Ando, Koichi Nishino, Okio Hino, Kazuhisa Takahashi, Kuniaki Seyama
Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant inherited disorder caused by germline mutations in the FLCN gene, and characterized by skin fibrofolliculomas, multiple lung cysts, spontaneous pneumothorax, and renal neoplasms. Pulmonary manifestations frequently develop earlier than other organ involvements, prompting a diagnosis of BHDS However, the mechanism of lung cyst formation and pathogenesis of pneumothorax have not yet been clarified. Fibroblasts were isolated from lung tissues obtained from patients with BHDS (n = 12) and lung cancer (n = 10) as controls...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27899647/spliceosomal-protein-eftud2-mutation-leads-to-p53-dependent-apoptosis-in-zebrafish-neural-progenitors
#4
Lei Lei, Shou-Yu Yan, Ran Yang, Jia-Yu Chen, Yumei Li, Ye Bu, Nannan Chang, Qinchao Zhou, Xiaojun Zhu, Chuan-Yun Li, Jing-Wei Xiong
Haploinsufficiency of EFTUD2 (Elongation Factor Tu GTP Binding Domain Containing 2) is linked to human mandibulofacial dysostosis, Guion-Almeida type (MFDGA), but the underlying cellular and molecular mechanisms remain to be addressed. We report here the isolation, cloning and functional analysis of the mutated eftud2 (snu114) in a novel neuronal mutant fn10a in zebrafish. This mutant displayed abnormal brain development with evident neuronal apoptosis while the development of other organs appeared less affected...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27894982/multiple-opportunistic-infections-in-a-woman-with-gata2-mutation
#5
Andrea Vila, Juan I Dapás, Cynthia V Rivero, Florencia Bocanegra, Roberto F Furnari, Amy P Hsu, Steven M Holland
GATA2 deficiency is a genetic disorder caused by inherited or sporadic haploinsufficient mutations in the GATA2 gene. Patients have abnormalities in hematopoiesis, lymphangiogenesis and immunity; encompassing a broad range of clinical syndromes, mainly characterized by monocytopenia, B and NK cell cytopenia, severe or recurrent infections, and a high risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).We report a case of an Argentinean woman, who presented with multiple opportunistic infections as her first manifestation of GATA2 deficiency...
November 25, 2016: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/27892983/association-of-mutations-in-tbk1-with-sporadic-and-familial-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia
#6
Axel Freischmidt, Kathrin Müller, Albert C Ludolph, Jochen H Weishaupt, Peter M Andersen
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are related neurodegenerative syndromes that occur sporadically or have been associated with mostly dominant inheritance of mutations in more than 30 genes. A critical issue is whether all reported mutations are disease causing or are coincidental findings. In this review we analyze the pathogenicity of nonsynonymous variants in the newly discovered gene encoding TANK-binding kinase 1 (TBK1). The available data suggest that mutations in TBK1 that cause a 50% reduction of TBK1 protein levels are pathogenic...
November 21, 2016: JAMA Neurology
https://www.readbyqxmd.com/read/27892953/thalamic-mir-338-3p-mediates-auditory-thalamocortical-disruption-and-its-late-onset-in-models-of-22q11-2-microdeletion
#7
Sungkun Chun, Fei Du, Joby J Westmoreland, Seung Baek Han, Yong-Dong Wang, Donnie Eddins, Ildar T Bayazitov, Prakash Devaraju, Jing Yu, Marcia M Mellado Lagarde, Kara Anderson, Stanislav S Zakharenko
Although 22q11.2 deletion syndrome (22q11DS) is associated with early-life behavioral abnormalities, affected individuals are also at high risk for the development of schizophrenia symptoms, including psychosis, later in life. Auditory thalamocortical (TC) projections recently emerged as a neural circuit that is specifically disrupted in mouse models of 22q11DS (hereafter referred to as 22q11DS mice), in which haploinsufficiency of the microRNA (miRNA)-processing-factor-encoding gene Dgcr8 results in the elevation of the dopamine receptor Drd2 in the auditory thalamus, an abnormal sensitivity of thalamocortical projections to antipsychotics, and an abnormal acoustic-startle response...
November 28, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27891178/enrichment-of-small-pathogenic-deletions-at-chromosome-9p24-3-and-9q34-3-involving-dock8-kank1-ehmt1-genes-identified-by-using-high-resolution-oligonucleotide-single-nucleotide-polymorphism-array-analysis
#8
Jia-Chi Wang, Loretta W Mahon, Leslie P Ross, Arturo Anguiano, Renius Owen, Fatih Z Boyar
BACKGROUND: High-resolution oligo-SNP array allowed the identification of extremely small pathogenic deletions at numerous clinically relevant regions. In our clinical practice, we found that small pathogenic deletions were frequently encountered at chromosome 9p and 9q terminal regions. RESULTS: A review of 531 cases with reportable copy number changes on chromosome 9 revealed142 pathogenic copy number variants (CNVs): 104 losses, 31 gains, 7 complex chromosomal rearrangements...
2016: Molecular Cytogenetics
https://www.readbyqxmd.com/read/27886408/role-of-rock2-in-cd4-cells-in-allergic-airways-responses-in-mice
#9
David I Kasahara, Joel A Mathews, Fernanda M C Ninin, Allison P Wurmbrand, James K Liao, Stephanie A Shore
BACKGROUND: Rho kinases (ROCKs) contribute to allergic airways disease. ROCKs also play a role in lymphocyte proliferation and migration. OBJECTIVE: To determine the role of ROCK2 acting within CD4(+) cells in allergic airways responses. METHODS: ROCK2 haploinsufficient (ROCK2(+/-) ) and wildtype mice were sensitized with ovalbumin (OVA). ROCK2(+/-) mice then received either CD4(+) cells from ROCK2 sufficient OVA TCR transgenic (OT-II) mice or saline i...
November 25, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27880066/features-of-kat6b-related-disorders-in-a-patient-with-10q22-1q22-3-deletion
#10
Egle Preiksaitiene, Birutė Tumienė, Živilė Maldžienė, Erinija Pranckevičienė, Aušra Morkūnienė, Algirdas Utkus, Vaidutis Kučinskas
BACKGROUND: Blepharophimosis is a fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures. It is a rare facial malformation and is considered an important diagnostic feature in dysmorphic analysis. It is likely that many patients with blepharophimosis-mental retardation syndrome have submicroscopic chromosomal rearrangements, and the use of molecular karyotyping can narrow the known blepharophimosis-mental retardation-critical regions or clarify the effect of the haploinsufficiency of the involved genes on the phenotype...
November 23, 2016: Ophthalmic Genetics
https://www.readbyqxmd.com/read/27879657/screening-for-mutations-in-the-tbx1-gene-on-chromosome-22q11-2-in-schizophrenia
#11
Lieh-Yung Ping, Yang-An Chuang, Shih-Hsin Hsu, Hsin-Yao Tsai, Min-Chih Cheng
A higher-than-expected frequency of schizophrenia in patients with 22q11.2 deletion syndrome suggests that chromosome 22q11.2 harbors the responsive genes related to the pathophysiology of schizophrenia. The TBX1 gene, which maps to the region on chromosome 22q11.2, plays a vital role in neuronal functions. Haploinsufficiency of the TBX1 gene is associated with schizophrenia endophenotype. This study aimed to investigate whether the TBX1 gene is associated with schizophrenia. We searched for mutations in the TBX1 gene in 652 patients with schizophrenia and 567 control subjects using a re-sequencing method and conducted a reporter gene assay...
November 22, 2016: Genes
https://www.readbyqxmd.com/read/27875309/rna-sequencing-reveals-a-role-of-tonebp-in-regulation-of-pro-inflammatory-genes-in-response-to-hyperosmolarity-in-healthy-nucleus-pulposus-cells-a-homeostatic-response
#12
Zariel I Johnson, Irving M Shapiro, Makarand V Risbud
Transcription factor Tonicity-Responsive Enhancer-Binding Protein (TonEBP/NFAT5) is critical for osmo-adaptation and extracellular matrix homeostasis of nucleus pulposus (NP) cells in their hypertonic tissue niche. Recent studies implicate TonEBP signaling in inflammatory disease and rheumatoid arthritis pathogenesis. However, broader functions of TonEBP in the disc remain unknown. RNA-sequencing was performed on NP cells with TonEBP knockdown under hypertonic conditions. 1140 TonEBP-dependent genes were identified and categorized using Ingenuity Pathway Analysis...
November 8, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27873163/an-update-on-the-use-of-immunomodulators-in-primary-immunodeficiencies
#13
REVIEW
Pandiarajan Vignesh, Amit Rawat, Surjit Singh
The genomic revolution in the past decade fuelled by breathtaking advances in sequencing technologies has defined several new genetic diseases of the immune system. Many of these newly characterized diseases are a result of defects in genes involved in immune regulation. The discovery of these diseases has opened a vista of new therapeutic possibilities. Immunomodulatory agents, a hitherto unexplored therapeutic option in primary immunodeficiency diseases have been tried in a host of these newly described maladies...
November 21, 2016: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/27870441/sexual-divergence-in-activity-dependent-neuroprotective-protein-impacting-autism-schizophrenia-and-alzheimer-s-disease
#14
REVIEW
Illana Gozes
Discovered in our laboratory, activity-dependent neuroprotective protein (ADNP) interacts with key regulatory proteins, including the chromatin remodeling complex SWI/SNF, proteins associated with RNA splicing, RNA translation, microtubule dynamics, and autophagy. ADNP regulates > 400 genes during mouse embryonic development and is essential for neural tube closure. ADNP key functions extend from mice to men, with mutations causing ADNP-related ID/autism syndrome, also known as the Helsmoortel-Van der Aa syndrome...
January 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27861891/opa1-haploinsufficiency-induces-a-bnip3-dependent-decrease-in-mitophagy-in-neurons-relevance-to-dominant-optic-atrophy
#15
Manon Moulis, Aurélie Millet, Marlène Daloyau, Marie-Christine Miquel, Brice Ronsin, Bernd Wissinger, Laetitia Arnauné-Pelloquin, Pascale Belenguer
Dominant Optic Atrophy (DOA) is due to mutations in the mitochondrial protein OPA1. The disease principally affects retinal ganglion cells, whose axons degenerate leading to vision impairments, and sometimes other neuronal phenotypes. The exact mechanisms underlying DOA pathogenesis are not known. We previously demonstrated that the main role of OPA1, as a mitochondrial fusogenic and anti-apoptotic protein, are inhibited by interaction with the stress inducible pro-apoptotic BNIP3 protein. Because BNIP3 was recently reported to participate in autophagy and mitophagy, we tested the involvement of these processes in DOA pathogenesis...
November 10, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27861793/a-novel-foxn1-egfp-mouse-model-identifies-bmp4-induced-maintenance-of-foxn1-expression-and-thymic-epithelial-progenitor-populations
#16
Marco Barsanti, Joanna M C Lim, Michael L Hun, Natalie Lister, Kahlia Wong, Maree V Hammett, Ailin Lepletier, Richard L Boyd, Antonietta Giudice, Ann P Chidgey
Although forkhead-box n1 (Foxn1) is a critical thymic epithelial cell regulator in thymus organogenesis, its association with epithelial differentiation and homeostasis in the postnatal and aged thymic microenvironment remains conflicting. Consequently, we have generated a Foxn1(eGFP/+) knock-in mouse model that allows for refined investigation of the aging thymic epithelium. This reporter line differs from those previously published in that concomitant expression of enhanced green fluorescent protein enables live cell sorting of Foxn1(+) cell populations...
November 10, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27861764/autosomal-recessive-variations-of-tbx6-from-congenital-scoliosis-to-spondylocostal-dysostosis
#17
M Lefebvre, Y Duffourd, T Jouan, C Poe, N Jean-Marçais, A Verloes, J St-Onge, J-B Riviere, F Petit, G Pierquin, B Demeer, P Callier, C Thauvin-Robinet, L Faivre, J Thevenon
Proximal 16p11.2 microdeletions are recurrent microdeletions with an overall prevalence of 0.03%. In patients with segmentation defects of the vertebra (SDV), a burden of this microdeletion was observed with TBX6 as a candidate gene for SDV. In a published cohort of patients with congenital scoliosis (CS), TBX6 haploinsufficiency was compound heterozygous with a common haplotype. Besides, a single three-generation family with spondylocostal dysostosis (SCD) was reported with a heterozygous stop-loss of TBX6...
November 8, 2016: Clinical Genetics
https://www.readbyqxmd.com/read/27860320/opa1-analysis-in-an-international-series-of-probands-with-bilateral-optic-atrophy
#18
Petra Liskova, Marketa Tesarova, Lubica Dudakova, Stepanka Svecova, Hana Kolarova, Tomas Honzik, Sharon Seto, Marcela Votruba
PURPOSE: To determine the molecular genetic cause in previously unreported probands with optic atrophy from the United Kingdom, Czech Republic and Canada. METHODS: OPA1 coding regions and flanking intronic sequences were screened by direct sequencing in 82 probands referred with a diagnosis of bilateral optic atrophy. Detected rare variants were assessed for pathogenicity by in silico analysis. Segregation of the identified variants was performed in available first degree relatives...
November 17, 2016: Acta Ophthalmologica
https://www.readbyqxmd.com/read/27860035/a-cell-type-specific-expression-signature-predicts-haploinsufficient-autism-susceptibility-genes
#19
Chaolin Zhang, Yufeng Shen
Recent studies have identified many genes with rare de novo mutations in autism, but a limited number of these have been conclusively established as disease-susceptibility genes due to lack of recurrence and confounding background mutations. Such extreme genetic heterogeneity severely limits recurrence-based statistical power even in studies with a large sample size. Here we use cell-type specific expression profiles to differentiate mutations in autism patients from those in unaffected siblings. We report a gene expression signature in different neuronal cell types shared by genes with likely gene disrupting (LGD) mutations in autism cases...
November 16, 2016: Human Mutation
https://www.readbyqxmd.com/read/27845235/haploinsufficiency-of-tnfaip3-a20-by-germline-mutation-is-involved-in-autoimmune-lymphoproliferative-syndrome
#20
Masatoshi Takagi, Shohei Ogata, Hiroo Ueno, Kenichi Yoshida, Tzuwen Yeh, Akihiro Hoshino, Jinhua Piao, Motoy Yamashita, Mai Nanya, Tsubasa Okano, Michiko Kajiwara, Hirokazu Kanegane, Hideki Muramatsu, Yusuke Okuno, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Yuki Bando, Motohiro Kato, Yasuhide Hayashi, Satoru Miyano, Kohsuke Imai, Seishi Ogawa, Seiji Kojima, Tomohiro Morio
BACKGROUND: Autoimmune diseases in children are rare and can be difficult to diagnose. Autoimmune lymphoproliferative syndrome (ALPS) is a well-characterized pediatric autoimmune disease caused by mutations in genes associated with the FAS-dependent apoptosis pathway. In addition, various genetic alterations are associated with the ALPS-like phenotype. OBJECTIVE: The aim of the present study was to elucidate the genetic etiology of the ALPS-like phenotype. METHODS: Candidate genes associated with the ALPS-like phenotype were screened by whole exome sequencing...
November 11, 2016: Journal of Allergy and Clinical Immunology
keyword
keyword
99368
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"