1,078 results match your criteria Dyskeratosis Congenita


Malignant Transformation of Buccal Mucosa Leukoplakia in a Patient With Dyskeratosis Congenita.

Ear Nose Throat J 2020 Jul 7:145561320938908. Epub 2020 Jul 7.

Department of Oral and Maxillofacial Surgery/Orthodontics, Yokohama City University Hospital, Kanazawa-ku, Yokohama, Kanagawa, Japan.

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http://dx.doi.org/10.1177/0145561320938908DOI Listing

Telomeres, p53, HNF4α, and Liver Disease.

Hepatology 2020 Jul 7. Epub 2020 Jul 7.

Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Dyskeratosis congenita is an inherited disorder characterized by defects in the ability of cells to maintain telomeres. Patients commonly present with pediatric bone marrow failure and liver and/or pulmonary fibrosis in the fourth to fifth decade of life. The prevalence of dyskeratosis congenita is estimated as 1 in 1 million; however, due to the incomplete penetrance of disease, the true prevalence is unknown. Read More

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http://dx.doi.org/10.1002/hep.31454DOI Listing

Nonsense Suppression Therapy: New Hypothesis for the Treatment of Inherited Bone Marrow Failure Syndromes.

Int J Mol Sci 2020 Jun 30;21(13). Epub 2020 Jun 30.

Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, P.le A. Stefani 1, 37126 Verona, Italy.

Inherited bone marrow failure syndromes (IBMFS) are a group of cancer-prone genetic diseases characterized by hypocellular bone marrow with impairment in one or more hematopoietic lineages. The pathogenesis of IBMFS involves mutations in several genes which encode for proteins involved in DNA repair, telomere biology and ribosome biogenesis. The classical IBMFS include Shwachman-Diamond syndrome (SDS), Diamond-Blackfan anemia (DBA), Fanconi anemia (FA), dyskeratosis congenita (DC), and severe congenital neutropenia (SCN). Read More

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http://dx.doi.org/10.3390/ijms21134672DOI Listing

Human RTEL1 associates with Poldip3 to facilitate responses to replication stress and R-loop resolution.

Genes Dev 2020 Jun 19. Epub 2020 Jun 19.

Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Science for Life Laboratory, Karolinska Institute, Solna 171 77, Sweden.

RTEL1 helicase is a component of DNA repair and telomere maintenance machineries. While RTEL1's role in DNA replication is emerging, how RTEL1 preserves genomic stability during replication remains elusive. Here we used a range of proteomic, biochemical, cell, and molecular biology and gene editing approaches to provide further insights into potential role(s) of RTEL1 in DNA replication and genome integrity maintenance. Read More

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http://dx.doi.org/10.1101/gad.330050.119DOI Listing

Chemical inhibition of PAPD5/7 rescues telomerase function and hematopoiesis in dyskeratosis congenita.

Blood Adv 2020 Jun;4(12):2717-2722

Department of Medicine and.

Dyskeratosis congenita (DC) is a pediatric bone marrow failure syndrome caused by germline mutations in telomere biology genes. Mutations in DKC1 (the most commonly mutated gene in DC), the 3' region of TERC, and poly(A)-specific ribonuclease (PARN) cause reduced levels of the telomerase RNA component (TERC) by reducing its stability and accelerating TERC degradation. We have previously shown that depleting wild-type DKC1 levels by RNA interference or expression of the disease-associated A353V mutation in the DKC1 gene leads to decay of TERC, modulated by 3'-end oligoadenylation by noncanonical poly(A) polymerase 5 (PAPD5) followed by 3' to 5' degradation by EXOSC10. Read More

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http://dx.doi.org/10.1182/bloodadvances.2020001848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322949PMC

Pseudouridylation defect due to and mutations causes nephrotic syndrome with cataracts, hearing impairment, and enterocolitis.

Proc Natl Acad Sci U S A 2020 Jun 17;117(26):15137-15147. Epub 2020 Jun 17.

MTA-SE Lendület Nephrogenetic Laboratory, Semmelweis University, HU 1083 Budapest, Hungary;

RNA modifications play a fundamental role in cellular function. Pseudouridylation, the most abundant RNA modification, is catalyzed by the H/ACA small ribonucleoprotein (snoRNP) complex that shares four core proteins, dyskerin (DKC1), NOP10, NHP2, and GAR1. Mutations in , , or cause dyskeratosis congenita (DC), a disorder characterized by telomere attrition. Read More

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http://dx.doi.org/10.1073/pnas.2002328117DOI Listing
June 2020
9.809 Impact Factor

A unique case of coats plus syndrome and dyskeratosis congenita in a patient with CTC1 mutations.

Ophthalmic Genet 2020 Jun 16:1-5. Epub 2020 Jun 16.

Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami , Miami, FL, USA.

Coats plus syndrome (CP) is a rare condition characterized by bilateral exudative retinal telangiectasias with associated systemic disorders primarily affecting the brain, bone and gastrointestinal tract due to a mutation in the gene. mutations are also known to cause dyskeratosis congenita (DC), which is an inherited bone marrow failure syndrome characterized by skin pigmentation abnormalities, nail dystrophy, and oral leukoplakia. This is the first reported case of a patient diagnosed with both CP and DC caused by compound heterozygous gene mutations. Read More

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http://dx.doi.org/10.1080/13816810.2020.1772315DOI Listing

Small Molecules Restore Telomeres in Patient Stem Cells.

Trends Pharmacol Sci 2020 May 29. Epub 2020 May 29.

Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

Genetic defects in telomere maintenance result in stem cell exhaustion and a spectrum of telomere biology diseases. Systemic treatments beyond organ transplantation are lacking for these diseases. Nagpal and colleagues identified small molecules that restore telomere maintenance in patient-derived stem cells, offering a promising therapy for telomere biology diseases. Read More

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http://dx.doi.org/10.1016/j.tips.2020.05.003DOI Listing

Familial retinal vessel tortuosity in dyskeratosis congenita.

Postgrad Med J 2020 May 28. Epub 2020 May 28.

General Medicine, Trivandrum Medical College, Thiruvananthapuram, Kerala 695011, India.

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http://dx.doi.org/10.1136/postgradmedj-2020-137958DOI Listing

CD8 T-cell senescence and skewed lymphocyte subsets in young Dyskeratosis Congenita patients with PARN and DKC1 mutations.

J Clin Lab Anal 2020 May 25:e23375. Epub 2020 May 25.

Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.

Background: Dyskeratosis congenita (DC) is a syndrome resulting from defective telomere maintenance. Immunodeficiency associated with DC can cause significant morbidity and lead to premature mortality, but the immunological characteristics and molecular hallmark of DC patients, especially young patients, have not been described in detail.

Methods: We summarize the clinical data of two juvenile patients with DC. Read More

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http://dx.doi.org/10.1002/jcla.23375DOI Listing
May 2020
1.144 Impact Factor

Impaired reproductive function and fertility preservation in a woman with a dyskeratosis congenita.

J Assist Reprod Genet 2020 May 13;37(5):1221-1225. Epub 2020 May 13.

Department of Obstetrics and Gynecology, New York University Langone Health, 550 First Avenue, NBV-9N1A, New York, NY, 10016, USA.

Purpose: To determine the impact of accelerated telomere shortening on the fertility parameters and treatment outcomes of a woman with dyskeratosis congenita (DKC).

Methods: A case study of the clinical data, blood, discarded oocytes, and arrested embryos of a woman with DKC and donated cryopreserved embryos from unaffected patients. Mean telomere length in blood cells was analyzed by flow cytometry-fluorescence in situ hybridization (flow-FISH) and qPCR. Read More

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http://dx.doi.org/10.1007/s10815-020-01758-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244669PMC

Regulation And Effect Of Telomerase And Telomeric Length In Stem Cells.

Curr Stem Cell Res Ther 2020 Apr 21. Epub 2020 Apr 21.

Address: Hacettepe University, Faculty of Medicine, Department of Medical Biochemistry, Sihhiye-Ankara. Turkey.

Telomeres are the protective end caps of eukaryotic chromosomes and they decide the proliferative lifespan of somatic cells, as the guardians of the cell replication. Telomere length in leucocytes reflects telomere length in other somatic cells. Leucocyte telomere length can be a biomarker of human ageing. Read More

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http://dx.doi.org/10.2174/1574888X15666200422104423DOI Listing

Small-Molecule PAPD5 Inhibitors Restore Telomerase Activity in Patient Stem Cells.

Cell Stem Cell 2020 Jun 21;26(6):896-909.e8. Epub 2020 Apr 21.

Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Stem Cell Institute, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Stem Cell Program, Boston Children's Hospital, Boston, MA, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA; Harvard Initiative in RNA Medicine, Boston, MA, USA. Electronic address:

Genetic lesions that reduce telomerase activity inhibit stem cell replication and cause a range of incurable diseases, including dyskeratosis congenita (DC) and pulmonary fibrosis (PF). Modalities to restore telomerase in stem cells throughout the body remain unclear. Here, we describe small-molecule PAPD5 inhibitors that demonstrate telomere restoration in vitro, in stem cell models, and in vivo. Read More

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http://dx.doi.org/10.1016/j.stem.2020.03.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275922PMC

Germline mutation of , a major p53 regulator, in a familial syndrome of defective telomere maintenance.

Sci Adv 2020 04 10;6(15):eaay3511. Epub 2020 Apr 10.

Genetics of Tumor Suppression, Institut Curie, Paris, France.

Dyskeratosis congenita is a cancer-prone inherited bone marrow failure syndrome caused by telomere dysfunction. A mouse model recently suggested that p53 regulates telomere metabolism, but the clinical relevance of this finding remained uncertain. Here, a germline missense mutation of , a negative regulator of p53, was found in a family with features suggestive of dyskeratosis congenita, e. Read More

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http://dx.doi.org/10.1126/sciadv.aay3511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148086PMC

OCT Angiography of Macular Telangiectasia in Dyskeratosis Congenita.

Ophthalmol Retina 2020 04;4(4):451

Retina Service, Department of Ophthalmology, Weill Cornell Medical College, New York, New York.

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http://dx.doi.org/10.1016/j.oret.2019.12.017DOI Listing

Regulation of human telomerase in homeostasis and disease.

Nat Rev Mol Cell Biol 2020 Jul 2;21(7):384-397. Epub 2020 Apr 2.

Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.

Telomerase is a ribonucleoprotein complex, the catalytic core of which includes the telomerase reverse transcriptase (TERT) and the non-coding human telomerase RNA (hTR), which serves as a template for the addition of telomeric repeats to chromosome ends. Telomerase expression is restricted in humans to certain cell types, and telomerase levels are tightly controlled in normal conditions. Increased levels of telomerase are found in the vast majority of human cancers, and we have recently begun to understand the mechanisms by which cancer cells increase telomerase activity. Read More

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http://dx.doi.org/10.1038/s41580-020-0234-zDOI Listing

Effective Multi-lineage Engraftment in a Mouse Model of Fanconi Anemia Using Non-genotoxic Antibody-Based Conditioning.

Mol Ther Methods Clin Dev 2020 Jun 8;17:455-464. Epub 2020 Feb 8.

Stem Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Conditioning chemotherapy is used to deplete hematopoietic stem cells in the recipient's marrow, facilitating donor cell engraftment. Although effective, a major issue with chemotherapy is the systemic genotoxicity that increases the risk for secondary malignancies. Antibody conjugates targeting hematopoietic cells are an emerging non-genotoxic method of opening the marrow niche and promoting engraftment of transplanted cells while maintaining intact marrow cellularity. Read More

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http://dx.doi.org/10.1016/j.omtm.2020.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096734PMC

Successful liver transplantation in short telomere syndromes without bone marrow failure due to DKC1 mutation.

Pediatr Transplant 2020 May 12;24(3):e13695. Epub 2020 Mar 12.

Division of Gastroenterology, Hepatology and Nutrition, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Short telomere syndromes are a heterogenous spectrum of disorders leading to premature cellular aging. These may involve bone marrow failure, adult-onset idiopathic pulmonary fibrosis, and liver disease, and classical entities such as dyskeratosis congenita. We report a patient who presented with common variable immunodeficiency at 3 years of age and autoimmune cytopenias at 8 years of age. Read More

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http://dx.doi.org/10.1111/petr.13695DOI Listing

TERT and TERC mutations detected in cryptic dyskeratosis congenita suppress telomerase activity.

Int J Lab Hematol 2020 Jun 9;42(3):316-321. Epub 2020 Mar 9.

Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan.

Introduction: A cryptic form of dyskeratosis congenita (cDKC) has a gradual onset without the characteristic physical findings of DKC. cDKC is distinguished from other forms of bone marrow failure (BMF) through analysis of telomere shortening and gene mutations. Mutations in the telomerase reverse transcriptase (TERT) and telomere RNA component (TERC) genes have been detected in most Japanese cDKC patients. Read More

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http://dx.doi.org/10.1111/ijlh.13176DOI Listing

Androgen therapy in inherited bone marrow failure syndromes: analysis from the Canadian Inherited Marrow Failure Registry.

Br J Haematol 2020 Jun 3;189(5):976-981. Epub 2020 Mar 3.

Division of Hematology/Oncology, Department of Pediatrics, Marrow Failure and Myelodysplasia Program, The Hospital for Sick Children, Toronto, ON, Canada.

Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood counts in different bone marrow failure conditions. Little is known about efficacy and toxicity with new androgens (i. Read More

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http://dx.doi.org/10.1111/bjh.16445DOI Listing

NHP2 deficiency impairs rRNA biogenesis and causes pulmonary fibrosis and Høyeraal-Hreidarsson syndrome.

Hum Mol Genet 2020 Apr;29(6):907-922

INSERM UMR 1163, Laboratory of Genome Dynamics in the Immune System, Equipe Labellisée La Ligue contre le Cancer, Paris, France.

Telomeres are nucleoprotein structures at the end of chromosomes. The telomerase complex, constituted of the catalytic subunit TERT, the RNA matrix hTR and several cofactors, including the H/ACA box ribonucleoproteins Dyskerin, NOP10, GAR1, NAF1 and NHP2, regulates telomere length. In humans, inherited defects in telomere length maintenance are responsible for a wide spectrum of clinical premature aging manifestations including pulmonary fibrosis (PF), dyskeratosis congenita (DC), bone marrow failure and predisposition to cancer. Read More

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http://dx.doi.org/10.1093/hmg/ddaa011DOI Listing

[The complex dental and oral surgical management with 8-year follow up of a Gorlin‒Goltz syndrome patient].

Orv Hetil 2020 Jan;161(2):67-74

Fogorvostudományi Kar, Arc-, Állcsont- és Szájsebészeti Tanszék, Pécsi Tudományegyetem, Klinikai Központ Pécs.

Gorlin-Goltz syndrome is an autosomal dominant hereditary disease. Its leading symptoms include keratocysts of the jaws, multiple basal cell carcinomas, skeletal abnormalities, intracranial calcifications and dyskeratosis of the soles and palms. One of the most common and often firstly discovered symptoms is the single or multiplex keratocysts of the jaws. Read More

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http://dx.doi.org/10.1556/650.2020.31566DOI Listing
January 2020

CNS manifestations in patients with telomere biology disorders.

Neurol Genet 2019 Dec 29;5(6):370. Epub 2019 Oct 29.

Clinical Genetics Branch (S.B., N.G., B.P.A., S.A.S.) and Biostatistics Branch (A.F.B.), Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville; Office of the Clinical Director (M.P.), National Institute of Mental Health, National Institutes of Health, Bethesda, MD; Department of Neurology (A.G.), Children's National Medical Center, Washington, DC; and Department of Radiology and Imaging Sciences (E.H.B.), Clinical Center, National Institutes of Health, Bethesda, MD.

Objective: We systematically evaluated CNS manifestations in patients with inherited telomere biology disorders (TBDs) to better understand the clinical and biological consequences of germline aberrations in telomere biology.

Methods: Forty-four participants with TBDs (31 dyskeratosis congenita, 12 Hoyeraal-Hreidarsson syndrome, and 1 Revesz syndrome) enrolled in an institutional review board-approved longitudinal cohort study underwent detailed clinical assessments, brain MRI, and genetic testing. Lymphocyte telomere length Z-scores were calculated to adjust for age. Read More

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http://dx.doi.org/10.1212/NXG.0000000000000370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878838PMC
December 2019

DKC1 enhances angiogenesis by promoting HIF-1α transcription and facilitates metastasis in colorectal cancer.

Br J Cancer 2020 Mar 20;122(5):668-679. Epub 2019 Dec 20.

Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.

Background: Dyskeratosis congenita 1 (DKC1) is dysregulated in several cancers. However, the expression and function of DKC1 in colorectal cancer (CRC) is rarely reported.

Methods: Tissue microarrays (TAMs) including 411 cases of CRC tissues and corresponding paracancerous tissues were used to examine the DKC1 expression. Read More

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http://dx.doi.org/10.1038/s41416-019-0695-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054532PMC
March 2020
4.836 Impact Factor

Monitoring and treatment of MDS in genetically susceptible persons.

Authors:
Stella M Davies

Hematology Am Soc Hematol Educ Program 2019 12;2019(1):105-109

Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Genetic susceptibility to myelodysplastic syndrome (MDS) occurs in children with inherited bone marrow failure syndromes, including Fanconi anemia, Shwachman Diamond syndrome, and dyskeratosis congenita. Available evidence (although not perfect) supports annual surveillance of the blood count and bone marrow in affected persons. Optimal treatment of MDS in these persons is most commonly transplantation. Read More

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http://dx.doi.org/10.1182/hematology.2019000020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913506PMC
December 2019

Prognostic significance of pulmonary function tests in dyskeratosis congenita, a telomere biology disorder.

ERJ Open Res 2019 Oct 15;5(4). Epub 2019 Nov 15.

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Pulmonary fibrosis and pulmonary arteriovenous malformations are known manifestations of dyskeratosis congenita (DC), a telomere biology disorder (TBD) and inherited bone marrow failure syndrome caused by germline mutations in telomere maintenance genes resulting in very short telomeres. Baseline pulmonary function tests (PFTs) and long-term clinical outcomes have not been thoroughly studied in DC/TBDs. In this retrospective study, 43 patients with DC and 67 unaffected relatives underwent baseline PFTs and were followed for a median of 8 years (range 1-14). Read More

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http://dx.doi.org/10.1183/23120541.00209-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856494PMC
October 2019

Dyskerin Mutations Present in Dyskeratosis Congenita Patients Increase Oxidative Stress and DNA Damage Signalling in .

Cells 2019 11 8;8(11). Epub 2019 Nov 8.

Instituto de Investigaciones Biomedicas, CSIC/UAM and Centro de Investigación Biomédica en Red de Enfermedades Raras, CIBERER, 28029 Madrid, Spain.

Dyskerin is a protein involved in the formation of small nucleolar and small Cajal body ribonucleoproteins. These complexes participate in RNA pseudouridylation and are also components of the telomerase complex required for telomere elongation. Dyskerin mutations cause a rare disease, X-linked dyskeratosis congenita, with no curative treatment. Read More

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http://dx.doi.org/10.3390/cells8111406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912284PMC
November 2019

Nopp140-mediated concentration of telomerase in Cajal bodies regulates telomere length.

Mol Biol Cell 2019 12 30;30(26):3136-3150. Epub 2019 Oct 30.

Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461.

Cajal bodies (CBs) are nuclear organelles concentrating two kinds of RNA--protein complexes (RNPs), spliceosomal small nuclear (sn), and small CB-specific (sca)RNPs. Whereas the CB marker protein coilin is responsible for retaining snRNPs, the tether for scaRNPs is not known. Here we show that Nopp140, an intrinsically disordered CB phosphoprotein, is required to recruit and retain all scaRNPs in CBs. Read More

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http://dx.doi.org/10.1091/mbc.E19-08-0429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938241PMC
December 2019

Comparison of flow-FISH and MM-qPCR telomere length assessment techniques for the screening of telomeropathies.

Ann N Y Acad Sci 2020 Apr 24;1466(1):93-103. Epub 2019 Oct 24.

Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, University Hospital Aachen, Aachen, Germany.

Assessment of telomere length (TL) in peripheral blood leukocytes is part of the diagnostic algorithm applied to patients with acquired bone marrow failure syndromes (BMFSs) and dyskeratosis congenita (DKC). Monochrome multiplex-quantitative polymerase chain reaction (MM-qPCR) and fluorescence in situ hybridization (flow-FISH) are methodologies available for TL screening. Dependent on TL expressed in relation to percentiles of healthy controls, further genetic testing for inherited mutations in telomere maintenance genes is recommended. Read More

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http://dx.doi.org/10.1111/nyas.14248DOI Listing
April 2020
1 Read

Copy Number Gain at Xq28 in a Child with Global Developmental Delay Associated with a Variant Form of Hoyeraal-Hreidarsson Syndrome.

Mol Syndromol 2019 Jul 27;10(4):214-218. Epub 2019 Apr 27.

Núcleo de Pesquisas Replicon, Departamento de Ciências Agrárias e Biológicas, Pontifícia Universidade Católica de Goiás, Goiânia, Brazil.

We report the case of a child from Central Brazil with global developmental delay (GDD), syndromic features, and absence of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa, with a rearrangement at Xq28 harboring the gene. GTC-banding revealed a male karyotype (46,XY) with no visible numerical or structural alterations. Chromosomal microarray analysis (CMA) showed a 0. Read More

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http://dx.doi.org/10.1159/000500005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738202PMC

Germline NPM1 mutations lead to altered rRNA 2'-O-methylation and cause dyskeratosis congenita.

Nat Genet 2019 10 30;51(10):1518-1529. Epub 2019 Sep 30.

Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

RNA modifications are emerging as key determinants of gene expression. However, compelling genetic demonstrations of their relevance to human disease are lacking. Here, we link ribosomal RNA 2'-O-methylation (2'-O-Me) to the etiology of dyskeratosis congenita. Read More

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http://dx.doi.org/10.1038/s41588-019-0502-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858547PMC
October 2019
2 Reads

NPM1 functions in epitranscriptomics.

Nat Genet 2019 10;51(10):1436-1437

Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.

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http://dx.doi.org/10.1038/s41588-019-0510-zDOI Listing
October 2019

Dyskeratosis Congenita.

Mayo Clin Proc 2019 09;94(9):1668-1669

Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine, Philadelphia; Department of Otorhinolaryngology: Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

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https://linkinghub.elsevier.com/retrieve/pii/S00256196193042
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http://dx.doi.org/10.1016/j.mayocp.2019.04.032DOI Listing
September 2019
4 Reads

Telomere dynamics and hematopoietic differentiation of human DKC1-mutant induced pluripotent stem cells.

Stem Cell Res 2019 10 20;40:101540. Epub 2019 Aug 20.

Department of Medical Imaging, Hematology, and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address:

Telomeropathies are a group of phenotypically heterogeneous diseases molecularly unified by pathogenic mutations in telomere-maintenance genes causing critically short telomeres. X-linked dyskeratosis congenita (DC), the prototypical telomere disease, manifested with ectodermal dysplasia, cancer predisposition, and severe bone marrow failure, is caused by mutations in DKC1, encoding a protein responsible for telomerase holoenzyme complex stability. To investigate the effects of pathogenic DKC1 mutations on telomere repair and hematopoietic development, we derived induced pluripotent stem cells (iPSCs) from fibroblasts of a DC patient carrying the most frequent mutation: DKC1 p. Read More

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http://dx.doi.org/10.1016/j.scr.2019.101540DOI Listing
October 2019
3 Reads

An update on the biology and management of dyskeratosis congenita and related telomere biology disorders.

Expert Rev Hematol 2019 12 10;12(12):1037-1052. Epub 2019 Sep 10.

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

: Telomere biology disorders (TBDs) encompass a group of illnesses caused by germline mutations in genes regulating telomere maintenance, resulting in very short telomeres. Possible TBD manifestations range from complex multisystem disorders with onset in childhood such as dyskeratosis congenita (DC), Hoyeraal-Hreidarsson syndrome, Revesz syndrome and Coats plus to adults presenting with one or two DC-related features.: The discovery of multiple genetic causes and inheritance patterns has led to the recognition of a spectrum of clinical features affecting multiple organ systems. Read More

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http://dx.doi.org/10.1080/17474086.2019.1662720DOI Listing
December 2019
5 Reads

From incomplete penetrance with normal telomere length to severe disease and telomere shortening in a family with monoallelic and biallelic PARN pathogenic variants.

Hum Mutat 2019 12 15;40(12):2414-2429. Epub 2019 Sep 15.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.

PARN encodes poly(A)-specific ribonuclease. Biallelic and monoallelic PARN variants are associated with Hoyeraal-Hreidarsson syndrome/dyskeratosis congenita and idiopathic pulmonary fibrosis (IPF), respectively. The molecular features associated with incomplete penetrance of PARN-associated IPF have not been described. Read More

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http://dx.doi.org/10.1002/humu.23898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874886PMC
December 2019
4 Reads
5.144 Impact Factor

Late presentation of dyskeratosis congenita.

Br J Haematol 2019 11 5;187(3):273. Epub 2019 Aug 5.

Division of Hematology, Stanford Cancer Institute/Stanford University School of Medicine, Stanford, CA, USA.

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http://dx.doi.org/10.1111/bjh.16131DOI Listing
November 2019
1 Read

Dyskeratosis Congenita and Corneal Refractive Surgery.

Ophthalmol Ther 2019 Sep 16;8(3):361-365. Epub 2019 Jul 16.

Hoopes Durrie Rivera Research Center, Hoopes Vision, Draper, UT, USA.

Dyskeratosis congenita is a syndrome of bone marrow failure secondary to unstable telomeres. It is characterized by a range of mucocutaneous diseases. Due to premature telomere shortening, these patients have limbal stem cell deficiency leading to poor regeneration and maintenance of the cornea. Read More

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http://dx.doi.org/10.1007/s40123-019-0200-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692790PMC
September 2019
3 Reads

Outcomes of Hematopoietic Cell Transplantation in Patients with Germline SAMD9/SAMD9L Mutations.

Biol Blood Marrow Transplant 2019 11 12;25(11):2186-2196. Epub 2019 Jul 12.

Division of Pediatric Hematology, Oncology and Blood and Marrow Transplantation, Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri. Electronic address:

Germline mutations in SAMD9 and SAMD9L genes cause MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) (OMIM: *610456) and ataxia-pancytopenia (OMIM: *611170) syndromes, respectively, and are associated with chromosome 7 deletions, myelodysplastic syndrome (MDS), and bone marrow failure. In this retrospective series, we report outcomes of allogeneic hematopoietic cell transplantation (HCT) in patients with hematologic disorders associated with SAMD9/SAMD9L mutations. Twelve patients underwent allogeneic HCT for MDS (n = 10), congenital amegakaryocytic thrombocytopenia (n = 1), and dyskeratosis congenita (n = 1). Read More

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http://dx.doi.org/10.1016/j.bbmt.2019.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110513PMC
November 2019
11 Reads

Impaired telomere integrity and rRNA biogenesis in PARN-deficient patients and knock-out models.

EMBO Mol Med 2019 07 6;11(7):e10201. Epub 2019 Jun 6.

Laboratory of Genome Dynamics in the Immune System, INSERM, UMR 1163, Paris, France.

PARN, poly(A)-specific ribonuclease, regulates the turnover of mRNAs and the maturation and stabilization of the hTR RNA component of telomerase. Biallelic PARN mutations were associated with Høyeraal-Hreidarsson (HH) syndrome, a rare telomere biology disorder that, because of its severity, is likely not exclusively due to hTR down-regulation. Whether PARN deficiency was affecting the expression of telomere-related genes was still unclear. Read More

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http://dx.doi.org/10.15252/emmm.201810201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609912PMC
July 2019
2 Reads

Complications for a Hoyeraal-Hreidarsson Syndrome Patient with a Germline A353V Variant Undergoing Unrelated Peripheral Blood Stem Cell Transplantation.

Int J Mol Sci 2019 Jul 2;20(13). Epub 2019 Jul 2.

Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.

Hoyeraal-Hreidarsson syndrome (HHS), caused by several different germline mutations resulting in severe telomeropathy, presents with early-onset growth anomalies and neurologic/developmental disorders including characteristic cerebellar hypoplasia. Early mortalities may arise from immunodeficiency and bone marrow failure if not successfully salvaged by allogeneic hematopoietic stem cell transplantation (HSCT). Few reports have characterized the persistent somatic progression of HHS after successful HSCT. Read More

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http://dx.doi.org/10.3390/ijms20133261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651050PMC
July 2019
7 Reads

The Role of Telomerase and Telomeres in Interstitial Lung Diseases: From Molecules to Clinical Implications.

Int J Mol Sci 2019 Jun 19;20(12). Epub 2019 Jun 19.

Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, P.O. Box 12000, Qiryat Hadassah, 91120 Jerusalem, Israel.

Telomeres are distal chromosome regions associated with specific protein complexes that protect the chromosome against degradation and aberrations. Telomere maintenance capacity is an essential indication of healthy cell populations, and telomere damage is observed in processes such as malignant transformation, apoptosis, or cell senescence. At a cellular level, telomere damage may result from genotoxic stress, decreased activity of telomerase enzyme complex, dysfunction of shelterin proteins, or changes in expression of telomere-associated RNA such as TERRA. Read More

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https://www.mdpi.com/1422-0067/20/12/2996
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http://dx.doi.org/10.3390/ijms20122996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627617PMC
June 2019
6 Reads

Hereditary myeloid malignancies.

Best Pract Res Clin Haematol 2019 06 3;32(2):163-176. Epub 2019 May 3.

Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

Myelodysplastic syndromes and acute myeloid leukemia are sporadic for the majority of cases affecting the elderly population. Inherited cases, however, do occur. Genetic predispositions to myeloid malignancies can be classified into three categories: familial cancer syndromes associated with increased risk of various malignancies including myelodysplasia and acute myeloid leukemia such as Li-Fraumeni syndrome and constitutional mismatch repair deficiency (CMMRD); germline mutations conferring a specific increased risk of myelodysplastic syndrome and acute myeloid leukemia such as mutations in ANKRD26, CEBPA, DDX41, ETV6, GATA2, RUNX1, SRP72 genes; and finally primarily pediatric inherited bone marrow failure syndromes such as Fanconi anemia, dyskeratosis congenita, severe congenital neutropenia, Shwachman-Diamond syndrome and Diamond Blackfan anemia. Read More

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http://dx.doi.org/10.1016/j.beha.2019.05.001DOI Listing
June 2019
21 Reads

Fatal Acute Exacerbation of Familial Interstitial Pneumonia Complicated with Dyskeratosis Congenita after Influenza Virus B Infection.

Intern Med 2019 Sep 7;58(18):2683-2687. Epub 2019 Jun 7.

Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan.

Dyskeratosis congenita (DC) is occasionally complicated in patients with familial interstitial pneumonia (FIP). However, there have been no reports of FIP patients with DC that develop acute exacerbation (AE). We herein report a FIP patient with DC that showed AE of FIP after influenza virus B infection. Read More

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http://dx.doi.org/10.2169/internalmedicine.2413-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794170PMC
September 2019
5 Reads

Telomerase insufficiency induced telomere erosion accumulation in successive generations in dyskeratosis congenita family.

Mol Genet Genomic Med 2019 07 22;7(7):e00709. Epub 2019 May 22.

Institute of Reproduction and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China.

Background: Dyskeratosis congenita (DC) is a rare heritable bone marrow failure syndrome that is associated with telomere dysfunction, and has high genetic heterogeneity and varied features.

Objective: This study aimed to identify the underlying genetic etiology of a DC family with more severe symptoms in the younger generation and to explore the relationship between the genetic causes and the severity of DC phenotype.

Methods: Whole-exome sequencing was performed on the proband to screen the candidate causative gene. Read More

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http://dx.doi.org/10.1002/mgg3.709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625126PMC
July 2019
10 Reads

Genetic and developmental disorders of the oral mucosa: Epidemiology; molecular mechanisms; diagnostic criteria; management.

Periodontol 2000 2019 06;80(1):12-27

WHO Collaboration Centre for Epidemiology and Community Dentistry, University of Milan, Milan, Italy.

A large number of disorders may affect the oral cavity, including genetic diseases, infections, cancers, blood diseases, skin diseases, endocrine and metabolic disorders, autoimmune and rheumatologic diseases, local lesions, to name a few. Oral mucosa shows a considerable variation in its normal structure and a wide range of conditions may affect it. Such conditions are often harmless or minor and could be primary or secondary to systemic disease. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1111/prd.12261
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http://dx.doi.org/10.1111/prd.12261DOI Listing
June 2019
39 Reads

Paracrine Interaction of Cancer Stem Cell Populations Is Regulated by the Senescence-Associated Secretory Phenotype (SASP).

Mol Cancer Res 2019 07 1;17(7):1480-1492. Epub 2019 May 1.

University of Illinois Cancer Center, Chicago, Illinois.

Dyskeratosis congenita is a telomere DNA damage syndrome characterized by defective telomere maintenance, bone marrow failure, and increased head and neck cancer risk. The mouse exhibits some features of dyskeratosis congenita, but head and neck cancer was not reported in this model. To model the head and neck cancer phenotype, we created unique Pot1b- and p53-null-mutant models which allow genetic lineage tracing of two distinct stem cell populations. Read More

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http://mcr.aacrjournals.org/lookup/doi/10.1158/1541-7786.MCR
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http://dx.doi.org/10.1158/1541-7786.MCR-18-1356DOI Listing
July 2019
9 Reads

Development of metachronous rectal cancers in a young man with dyskeratosis congenita: a case report.

J Med Case Rep 2019 Apr 27;13(1):117. Epub 2019 Apr 27.

Department of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan.

Background: DKC1 (dyskerin pseudouridine synthase 1) is a causative gene for X-linked dyskeratosis congenita. Approximately 8% of patients with dyskeratosis congenita have malignancy, but information about the development of malignancy in patients with dyskeratosis congenita is limited.

Case Presentation: A young Japanese patient with bone marrow failure developed metachronous rectal adenocarcinomas at the ages of 16 and 18 years. Read More

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http://dx.doi.org/10.1186/s13256-019-2044-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486685PMC
April 2019
5 Reads

Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes.

Orphanet J Rare Dis 2019 04 17;14(1):82. Epub 2019 Apr 17.

Instituto de Investigaciones Biomedicas CSIC/UAM, IDIPaz, Arturo Duperier, 4, 28029, Madrid, Spain.

Background: Telomeres are nucleoprotein structures present at the terminal region of the chromosomes. Mutations in genes coding for proteins involved in telomere maintenance are causative of a number of disorders known as telomeropathies. The genetic origin of these diseases is heterogeneous and has not been determined for a significant proportion of patients. Read More

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https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1
Publisher Site
http://dx.doi.org/10.1186/s13023-019-1046-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471801PMC
April 2019
37 Reads