keyword
https://read.qxmd.com/read/37853975/compound-heterozygous-mutations-in-the-helicase-rtel1-causing-hoyeraal-hreidarsson-syndrome-with-blake-s-pouch-cyst-a-case-report
#21
Min He, GuoLi Lian, HaiPeng Hu, Huan He, Miaomiao Wang
BACKGROUND: Telomeres inhibit DNA damage response at the ends of the chromosome to suppress cell cycle arrest as well as ensure genome stability. Dyskeratosis congenita (DC), a telomere-related disease, includes the classical triad involving oral leukoplakia, dysplastic nails, and lacy reticular pigment in the neck and/or upper chest. Hoyeraal-Hreidarrson syndrome (HHS), a severe manifestation of DC, frequently occurs during childhood, and patients with HHS often show short-term survival and thus do not exhibit all mucocutaneous manifestations or syndromic features...
2023: Turkish Journal of Pediatrics
https://read.qxmd.com/read/37834388/p53-in-the-molecular-circuitry-of-bone-marrow-failure-syndromes
#22
REVIEW
Jeanne Rakotopare, Franck Toledo
Mice with a constitutive increase in p53 activity exhibited features of dyskeratosis congenita (DC), a bone marrow failure syndrome (BMFS) caused by defective telomere maintenance. Further studies confirmed, in humans and mice, that germline mutations affecting TP53 or its regulator MDM4 may cause short telomeres and alter hematopoiesis, but also revealed features of Diamond-Blackfan anemia (DBA) or Fanconi anemia (FA), two BMFSs, respectively, caused by defects in ribosomal function or DNA repair. p53 downregulates several genes mutated in DC, either by binding to promoter sequences ( DKC1 ) or indirectly via the DREAM repressor complex ( RTEL1 , DCLRE1B ), and the p53-DREAM pathway represses 22 additional telomere-related genes...
October 6, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/37787873/genetic-counseling-and-family-screening-recommendations-in-patients-with-telomere-biology-disorders
#23
REVIEW
Laura Ongie, Hannah A Raj, Katie Barrett Stevens
PURPOSE OF REVIEW: Telomere biology disorders (TBDs) encompass a spectrum of genetic diseases with a common pathogenesis of defects in telomerase function and telomere maintenance causing extremely short telomere lengths. Here, we review the current literature surrounding genetic testing strategies, cascade testing, reproductive implications, and the role of genetic counseling. RECENT FINDINGS: The understanding of the genetic causes and clinical symptoms of TBDs continues to expand while genetic testing and telomere length testing are nuanced tools utilized in the diagnosis of this condition...
October 3, 2023: Current Hematologic Malignancy Reports
https://read.qxmd.com/read/37761906/new-insights-into-dyskerin-cypa-interaction-implications-for-x-linked-dyskeratosis-congenita-and-beyond
#24
JOURNAL ARTICLE
Valentina Belli, Daniela Maiello, Concetta Di Lorenzo, Maria Furia, Rosario Vicidomini, Mimmo Turano
The highly conserved family of cyclophilins comprises multifunctional chaperones that interact with proteins and RNAs, facilitating the dynamic assembly of multimolecular complexes involved in various cellular processes. Cyclophilin A (CypA), the predominant member of this family, exhibits peptidyl-prolyl cis-trans isomerase activity. This enzymatic function aids with the folding and activation of protein structures and often serves as a molecular regulatory switch for large multimolecular complexes, ensuring appropriate inter- and intra-molecular interactions...
September 6, 2023: Genes
https://read.qxmd.com/read/37737237/telomerase-rna-based-aptamers-restore-defective-myelopoiesis-in-congenital-neutropenic-syndromes
#25
JOURNAL ARTICLE
Elena Martínez-Balsalobre, Jesús García-Castillo, Diana García-Moreno, Elena Naranjo-Sánchez, Miriam Fernández-Lajarín, María A Blasco, Francisca Alcaraz-Pérez, Victoriano Mulero, María L Cayuela
Telomerase RNA (TERC) has a noncanonical function in myelopoiesis binding to a consensus DNA binding sequence and attracting RNA polymerase II (RNA Pol II), thus facilitating myeloid gene expression. The CR4/CR5 domain of TERC is known to play this role, since a mutation of this domain found in dyskeratosis congenita (DC) patients decreases its affinity for RNA Pol II, impairing its myelopoietic activity as a result. In this study, we report that two aptamers, short single-stranded oligonucleotides, based on the CR4/CR5 domain were able to increase myelopoiesis without affecting erythropoiesis in zebrafish...
September 22, 2023: Nature Communications
https://read.qxmd.com/read/37717172/crispr-screen-identifies-cebpb-as-contributor-to-dyskeratosis-congenita-fibroblast-senescence-via-augmented-inflammatory-gene-response
#26
JOURNAL ARTICLE
Erik R Westin, Alireza Khodadadi-Jamayran, Linh K Pham, Moon Ley Tung, Frederick D Goldman
Aging is the consequence of intra- and extracellular events that promote cellular senescence. Dyskeratosis congenita (DC) is an example of a premature aging disorder caused by underlying telomere/telomerase-related mutations. Cells from these patients offer an opportunity to study telomere-related aging and senescence. Our previous work has found that telomere shortening stimulates DNA damage responses (DDR) and increases reactive oxygen species (ROS), thereby promoting entry into senescence. This work also found that telomere elongation via TERT expression, the catalytic component of the telomere-elongating enzyme telomerase, or p53 shRNA could decrease ROS by disrupting this telomere-DDR-ROS pathway...
September 17, 2023: G3: Genes—Genomes—Genetics
https://read.qxmd.com/read/37684150/ac125611-3-promotes-the-progression-of-colon-cancer-by-recruiting-dkc1-to-stabilize-ctnnb1
#27
JOURNAL ARTICLE
Hanqing Tang, Yuyu Dou, Yiliang Meng, Qinglan Lu, Lingling Liang
BACKGROUND AND STUDY AIMS: Previous studies have suggested that lncRNAs impact cancer progression. The lncRNA AC125611.3 (also referred to as RP11-161H23.5) is highly expressed in colon cancer but rarely studied; understanding its regulation may provide novel insights on treating colon cancer. MATERIALS AND METHODS: qRT-PCR was performed to quantify RNAs. CCK-8 and EdU assays were performed to assess cell proliferation. Western blot analysis was used to detect levels of proteins related to cell apoptosis and EMT...
September 6, 2023: Arab Journal of Gastroenterology: the Official Publication of the Pan-Arab Association of Gastroenterology
https://read.qxmd.com/read/37661832/a-systematic-approach-identifies-p53-dream-target-genes-associated-with-blood-or-brain-abnormalities
#28
JOURNAL ARTICLE
Jeanne Rakotopare, Vincent Lejour, Carla Duval, Eliana Eldawra, Hugues Escoffier, Franck Toledo
p53 is a tumor suppressor, but mouse models revealed that increased p53 activity may cause bone marrow failure, likely through DREAM-mediated gene repression. Here we designed a systematic approach to identify p53-DREAM targets whose repression might contribute to abnormal hematopoiesis. We used gene ontology to analyze transcriptomic changes associated with bone marrow cell differentiation, then ChIP-seq data to identify DREAM-bound promoters. We next created positional frequency matrices to identify evolutionary conserved sequence elements potentially bound by DREAM...
September 1, 2023: Disease Models & Mechanisms
https://read.qxmd.com/read/37627314/the-molecular-and-genetic-mechanisms-of-inherited-bone-marrow-failure-syndromes-the-role-of-inflammatory-cytokines-in-their-pathogenesis
#29
REVIEW
Nozomu Kawashima, Valentino Bezzerri, Seth J Corey
Inherited bone marrow failure syndromes (IBMFSs) include Fanconi anemia, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, dyskeratosis congenita, severe congenital neutropenia, and other rare entities such as GATA2 deficiency and SAMD9/9L mutations. The IBMFS monogenic disorders were first recognized by their phenotype. Exome sequencing has validated their classification, with clusters of gene mutations affecting DNA damage response (Fanconi anemia), ribosome structure (Diamond-Blackfan anemia), ribosome assembly (Shwachman-Diamond syndrome), or telomere maintenance/stability (dyskeratosis congenita)...
August 16, 2023: Biomolecules
https://read.qxmd.com/read/37593443/dyskeratosis-congenita-natural-history-of-the-disease-through-the-study-of-a-cohort-of-patients-diagnosed-in-childhood
#30
JOURNAL ARTICLE
M L Uria-Oficialdegui, S Navarro, L Murillo-Sanjuan, C Rodriguez-Vigil, M I Benitez-Carbante, C Blazquez-Goñi, J A Salinas, C Diaz-de-Heredia
BACKGROUND: Dyskeratosis congenita (DC) is a multisystem and ultra-rare hereditary disease characterized by somatic involvement, bone marrow failure, and predisposition to cancer. The main objective of this study is to describe the natural history of DC through a cohort of patients diagnosed in childhood and followed up for a long period of time. MATERIAL AND METHODS: Multicenter, retrospective, longitudinal study conducted in patients followed up to 24 years since being diagnosed in childhood (between 1998 and 2020)...
2023: Frontiers in Pediatrics
https://read.qxmd.com/read/37544646/the-parn-toe1-and-usb1-rna-deadenylases-and-their-roles-in-non-coding-rna-regulation
#31
REVIEW
Thao Ngoc Huynh, Roy Parker
The levels of non-coding RNAs (ncRNAs) are regulated by transcription, RNA processing, and RNA degradation pathways. One mechanism for the degradation of ncRNAs involves the addition of oligo(A) tails by noncanonical poly(A) polymerases, which then recruit processive sequence-independent 3' to 5' exonucleases for RNA degradation. This pathway of decay is also regulated by three 3' to 5' exoribonucleases, USB1, PARN, and TOE1, which remove oligo(A) tails and thereby can protect ncRNAs from decay in a manner analogous to the deubiquination of proteins...
August 4, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37507252/inherited-bone-marrow-failure-syndromes-and-germline-predisposition-to-myeloid-neoplasia-a-practical-approach-for-the-pathologist
#32
REVIEW
Jingwei Li, Jacob R Bledsoe
The diagnostic work up and surveillance of germline disorders of bone marrow failure and predisposition to myeloid malignancy is complex and involves correlation between clinical findings, laboratory and genetic studies, and bone marrow histopathology. The rarity of these disorders and the overlap of clinical and pathologic features between primary and secondary causes of bone marrow failure, acquired aplastic anemia, and myelodysplastic syndrome may result in diagnostic uncertainty. With an emphasis on the pathologist's perspective, we review diagnostically useful features of germline disorders including Fanconi anemia, Shwachman-Diamond syndrome, telomere biology disorders, severe congenital neutropenia, GATA2 deficiency, SAMD9/SAMD9L diseases, Diamond-Blackfan anemia, and acquired aplastic anemia...
November 2023: Seminars in Diagnostic Pathology
https://read.qxmd.com/read/37506213/control-of-protein-synthesis-through-mrna-pseudouridylation-by-dyskerin
#33
JOURNAL ARTICLE
Chiara Pederiva, Davide M Trevisan, Dimitra Peirasmaki, Shan Chen, Sharon A Savage, Ola Larsson, Jernej Ule, Laura Baranello, Federico Agostini, Marianne Farnebo
Posttranscriptional modifications of mRNA have emerged as regulators of gene expression. Although pseudouridylation is the most abundant, its biological role remains poorly understood. Here, we demonstrate that the pseudouridine synthase dyskerin associates with RNA polymerase II, binds to thousands of mRNAs, and is responsible for their pseudouridylation, an action that occurs in chromatin and does not appear to require a guide RNA with full complementarity. In cells lacking dyskerin, mRNA pseudouridylation is reduced, while at the same time, de novo protein synthesis is enhanced, indicating that this modification interferes with translation...
July 28, 2023: Science Advances
https://read.qxmd.com/read/37496551/dyskeratosis-congenita-a-case-report-of-a-patient-with-coronary-artery-disease
#34
Michael Ghaly, Mark Ghaly, Samuel Harris
Clinical evidence demonstrates that patients with telomere biology disorders, such as dyskeratosis congenita, are more prone to coronary artery disease. We present the case of a 43-year-old female diagnosed with dyskeratosis congenita with critical cardiovascular disease. She underwent coronary artery bypass graft (CABG) with improvement of her cardiac function. Although this is a rare genetic disease, further studies are warranted to investigate the underlying pathophysiology of cardiovascular disease in patients with dyskeratosis congenita...
June 2023: Curēus
https://read.qxmd.com/read/37372478/inherited-reticulate-pigmentary-disorders
#35
REVIEW
Min-Huei Lin, Pei-Chen Chou, I-Chen Lee, Syuan-Fei Yang, Hsin-Su Yu, Sebastian Yu
Reticulate pigmentary disorders (RPDs) are a group of inherited and acquired skin conditions characterized by hyperpigmented and/or hypopigmented macules. Inherited RPDs include dyschromatosis symmetrica hereditaria (DSH), dyschromatosis universalis hereditaria (DUH), reticulate acropigmentation of Kitamura (RAK), Dowling-Degos disease (DDD), dyskeratosis congenita (DKC), Naegeli-Franceschetti-Jadassohn syndrome (NFJS), dermatopathia pigmentosa reticularis (DPR), and X-linked reticulate pigmentary disorder...
June 20, 2023: Genes
https://read.qxmd.com/read/37354000/the-distribution-and-accumulation-of-the-shortest-telomeres-in-telomere-biology-disorders
#36
JOURNAL ARTICLE
Hannah A Raj, Tsung-Po Lai, Marena R Niewisch, Neelam Giri, Youjin Wang, Stephen R Spellman, Abraham Aviv, Shahinaz M Gadalla, Sharon A Savage
Individuals with telomere biology disorders (TBDs) have very short telomeres, high risk of bone marrow failure (BMF), and reduced survival. Using data from TBD patients, a mean leukocyte Southern blot telomere length (TL) of 5 kilobases (kb) was estimated as the 'telomere brink' at which human survival is markedly reduced. However, the shortest telomere, not the mean TL, signals replicative senescence. We used the Telomere Shortest Length Assay (TeSLA) to tally TL of all 46 chromosomes in blood-derived DNA and examined its relationship with TBDs...
June 24, 2023: British Journal of Haematology
https://read.qxmd.com/read/37302654/patient-induced-pluripotent-stem-cell-derived-hepatostellate-organoids-establish-a-basis-for-liver-pathologies-in-telomeropathies
#37
JOURNAL ARTICLE
Young-Jun Choi, Melissa S Kim, Joshua H Rhoades, Nicolette M Johnson, Corbett T Berry, Sarah Root, Qijun Chen, Yuhua Tian, Rafael J Fernandez, Zvi Cramer, Stephanie Adams-Tzivelekidis, Ning Li, F Brad Johnson, Christopher J Lengner
BACKGROUND & AIMS: Dyskeratosis congenita (DC) is a telomere maintenance disorder caused primarily by mutations in the DKC1 gene. Patients with DC and related telomeropathies resulting from premature telomere dysfunction suffer from multi-organ failure. In the liver, DC patients present with nodular hyperplasia, steatosis, inflammation, and cirrhosis. However, the mechanism responsible for telomere dysfunction-induced liver disease remains unclear. METHODS: We used isogenic human induced pluripotent stem (iPS) cells harboring a causal DC mutation in DKC1, or a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-corrected control allele to model DC liver pathologies...
June 9, 2023: Cellular and Molecular Gastroenterology and Hepatology
https://read.qxmd.com/read/37259830/hematopoietic-cell-transplantation-for-telomere-biology-diseases-a-retrospective-single-center-cohort-study
#38
JOURNAL ARTICLE
Samantha Nichele, Carmem Bonfim, Luiz G D Junior, Gisele Loth, Cilmara Kuwahara, Joanna Trennephol, Vaneuza A M Funke, Daniela E Marinho, Adriana Koliski, Adriana M Rodrigues, Rebeca T G Mousquer, Anders Fasth, Alberto C M Lima, Rodrigo T Calado, Ricardo Pasquini
BACKGROUND: Telomere biology diseases (TBD) result from defective telomere maintenance, leading to bone marrow failure. The only curative treatment for aplastic anemia related to TBD is a hematopoietic cell transplant (HCT). Although reduced-intensity conditioning (RIC) regimens decrease transplant-related mortality, non-hematological phenotypes represent a major challenge and are associated with poor long-term follow-up outcomes. OBJECTIVE: To describe the outcome of TBD patients transplanted for marrow failure...
June 1, 2023: European Journal of Haematology
https://read.qxmd.com/read/37246821/spectrum-of-liver-pathology-in-dyskeratosis-congenita
#39
JOURNAL ARTICLE
Juan Putra, Suneet Agarwal, Alyaa Al-Ibraheemi, Ahmad I Alomari, Antonio R Perez-Atayde
Dyskeratosis congenita (DC) is a rare multisystemic disorder associated with defective telomere maintenance. Frequent clinical manifestations of DC include reticular skin pigmentation, dystrophic nails, oral leukoplakia, and bone marrow failure. Hepatic disturbances are reported to occur in 7% of DC patients. This study aimed to evaluate the histopathologic spectrum of hepatic involvement in this disorder. DC patients with liver tissue in the pathology database at Boston Children's Hospital from 1995 to 2022 were identified...
May 29, 2023: American Journal of Surgical Pathology
https://read.qxmd.com/read/37200733/endoscopic-assessment-and-serial-balloon-dilatation-in-a-toddler-with-dyskeratosis-congenita-hoyeraal-hreidarsson-syndrome-following-bone-marrow-transplant-a-case-report
#40
Kurt Rodriguez, Ryan Shargo, Morgan Ekblad, Gauri Sunkersett, Sara Karjoo, Marisol Betensky, Michael J Wilsey
We report a 3-year-old patient with suspected oropharyngeal graft-versus-host disease (GVHD) who developed progressive dysphagia to solids and liquids. The patient has a history of Dyskeratosis Congenita-Hoyeraal-Hreidarsson Syndrome with associated bone marrow failure requiring a nonmyeloablative matched sibling hematopoietic stem cell transplant. Esophagram revealed significant narrowing in the cricopharyngeal region. Subsequent esophagoscopy showed a proximal, high-grade pinhole esophageal stricture that was very difficult to visualize and cannulate...
May 2023: JPGN reports
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