1,014 results match your criteria Dyskeratosis Congenita


The RNase PARN Controls the Levels of Specific miRNAs that Contribute to p53 Regulation.

Mol Cell 2019 Feb 8. Epub 2019 Feb 8.

Department of Biochemistry, University of Colorado, Boulder, CO 80303, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address:

PARN loss-of-function mutations cause a severe form of the hereditary disease dyskeratosis congenita (DC). PARN deficiency affects the stability of non-coding RNAs such as human telomerase RNA (hTR), but these effects do not explain the severe disease in patients. We demonstrate that PARN deficiency affects the levels of numerous miRNAs in human cells. Read More

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http://dx.doi.org/10.1016/j.molcel.2019.01.010DOI Listing
February 2019

Posttranscriptional modulation of TERC by PAPD5 inhibition rescues hematopoietic development in dyskeratosis congenita.

Blood 2019 Feb 6. Epub 2019 Feb 6.

Center of Regenerative Medicine, Washington University in St. Louis, St. Louis, MO, United States

Reduced levels of , the telomerase RNA component, cause dyskeratosis congenita (DC) in patients harboring mutations in TERC, PARN, NOP10, NHP2, NAF1, or DKC1. Inhibition of the non-canonical poly(A) polymerase , or the exosome RNA degradation complex, partially restores levels in immortalized DKC1 mutant cells, but it remains unknown if modulation of posttranscriptional processing of could improve hematopoietic output in dyskeratosis congenita. We used human embryonic stem cells (hESCs) with a common dyskerin mutation (DKC1_A353V), which have defective telomere maintenance and reduced definitive hematopoietic potential, to understand the effects of reducing EXOSC3 activity, or silencing PAPD5-mediated oligoadenylation, on hematopoietic progenitor specification and function in DC. Read More

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http://dx.doi.org/10.1182/blood-2018-11-885368DOI Listing
February 2019

[Research progress of dyskeratosis congenita].

Zhonghua Kou Qiang Yi Xue Za Zhi 2019 Feb;54(2):130-134

Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University & State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Chengdu 610041, China.

Dyskeratosis congenita (DC) is a rare disease and a genetic heterogeneity of bone marrow failure, characterized by muco-cutaneous triad of mucosal leukoplakia, abnormal skin pigmentation, nails dystrophy and often involving multiple organs or systems. The inheritance patterns of DC include X-linked recessive, autosomal dominant and recessive patterns. However, the inheritance patterns in 30%-40% of DC patients remained unknown. Read More

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http://dx.doi.org/10.3760/cma.j.issn.1002-0098.2019.02.010DOI Listing
February 2019
2 Reads

GSE4 peptide suppresses oxidative and telomere deficiencies in ataxia telangiectasia patient cells.

Cell Death Differ 2019 Jan 22. Epub 2019 Jan 22.

Instituto de Investigaciones Biomédicas CSIC/UAM, IDiPaz, C/ Arturo Duperier, 4, 28029, Madrid, Spain.

Ataxia telangiectasia (AT) is a genetic disease caused by mutations in the ATM gene but the mechanisms underlying AT are not completely understood. Key functions of the ATM protein are to sense and regulate cellular redox status and to transduce DNA double-strand break signals to downstream effectors. ATM-deficient cells show increased ROS accumulation, activation of p38 protein kinase, and increased levels of DNA damage. Read More

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http://dx.doi.org/10.1038/s41418-018-0272-7DOI Listing
January 2019
1 Read

Extensive erosion instead of leukoplakia can be the oral manifestation of dyskeratosis congenita.

Oral Dis 2019 Jan 8. Epub 2019 Jan 8.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1111/odi.13035DOI Listing
January 2019
1 Read

Clinical features of dyskeratosis congenita in mainland China: case reports and literature review.

Int J Hematol 2019 Jan 3. Epub 2019 Jan 3.

Department of Pediatrics, Tongji Hospital, Tongji University School of Medicine, Xincun Road 389, Shanghai, 200065, People's Republic of China.

Dyskeratosis congenita (DC) is a rare-inherited bone marrow failure syndrome associated with multi-system disorder. To summarize the clinical features, epidemiology, and treatment of DC in mainland China, we retrospectively reviewed the medical records of two patients diagnosed with DC at our hospital and published reports on other DC patients in mainland China. The clinical features of 82 DC patients were summarized. Read More

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http://dx.doi.org/10.1007/s12185-018-02582-xDOI Listing
January 2019
3 Reads
1.679 Impact Factor

Squamous cell carcinoma of the tongue in a patient with dyskeratosis congenita: a rare entity.

Br J Oral Maxillofac Surg 2019 Jan 23;57(1):79-81. Epub 2018 Dec 23.

Tata Memorial Hospital, Parel Mumbai, 400012.

Dyskeratosis congenita is a rare genetic disorder that results from progressive failure of the bone marrow. It presents with a classic triad of reticular pigmentations of the skin, dystrophic nails, and oral leukoplakia; patients rarely develop cancers. We report a patient with dyskeratosis congenita who presented with squamous cell carcinoma of the oral tongue. Read More

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http://dx.doi.org/10.1016/j.bjoms.2018.12.002DOI Listing
January 2019
5 Reads

Peering through zebrafish to understand inherited bone marrow failure syndromes.

Haematologica 2019 Jan 20;104(1):13-24. Epub 2018 Dec 20.

Department of Pediatrics, Children's Hospital of Richmond and Massey Cancer Center at Virginia Commonwealth University, Richmond, VA, USA

Inherited bone marrow failure syndromes are experiments of nature characterized by impaired hematopoiesis with cancer and leukemia predisposition. The mutations associated with inherited bone marrow failure syndromes affect fundamental cellular pathways, such as DNA repair, telomere maintenance, or proteostasis. How these disturbed pathways fail to produce sufficient blood cells and lead to leukemogenesis are not understood. Read More

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http://dx.doi.org/10.3324/haematol.2018.196105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312012PMC
January 2019
2 Reads

Acquired and germline predisposition to bone marrow failure: Diagnostic features and clinical implications.

Semin Hematol 2019 Jan 23;56(1):69-82. Epub 2018 Jun 23.

Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, 20892 MD, USA. Electronic address:

Bone marrow failure and related syndromes are rare disorders characterized by ineffective bone marrow hematopoiesis and peripheral cytopenias. Although many are associated with characteristic clinical features, recent advances have shown a more complicated picture with a spectrum of broad and overlapping phenotypes and imperfect genotype-phenotype correlations. Distinguishing acquired from inherited forms of marrow failure can be challenging, but is of crucial importance given differences in the risk of disease progression to myelodysplastic syndrome, acute myeloid leukemia, and other malignancies, as well as the potential to genetically screen relatives and select the appropriate donor if hematopoietic stem cell transplantation becomes necessary. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00371963183006
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http://dx.doi.org/10.1053/j.seminhematol.2018.05.016DOI Listing
January 2019
8 Reads

Dyskeratosis congenita: presentation of cutaneous triad in a sporadic case.

BMJ Case Rep 2018 Nov 28;11(1). Epub 2018 Nov 28.

Department of Surgery, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India.

Dyskeratosis congenita (DKC) also known as Zinsser-Cole-Engman syndrome is a progressive genetic disease with a classical presentation characterised by a triad of reticulate pigmentation of skin, nail dystrophy and leukoplakia. It may be a multisystem disease with the involvement of haematological, gastrointestinal, genitourinary, neurological, ophthalmic, pulmonary and skeletal system. We report a sporadic case of DKC presenting with poikiloderma, nail dystrophy and oral leukoplakia. Read More

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http://dx.doi.org/10.1136/bcr-2018-226736DOI Listing
November 2018
2 Reads

Novel mutation of the TINF2 gene resulting in severe phenotypic Revesz syndrome.

Pediatr Blood Cancer 2019 Mar 26;66(3):e27557. Epub 2018 Nov 26.

Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

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http://dx.doi.org/10.1002/pbc.27557DOI Listing
March 2019
1 Read

Long-Term Follow-Up of a Case with Dyskeratosis Congenita Caused by NHP2-V126M/X154R Mutation: Genotype-Phenotype Association.

Acta Haematol 2019 23;141(1):28-31. Epub 2018 Nov 23.

Department of Pediatric Hematology, Dokuz Eylül University Faculty of Medicine, İzmir,

Dyskeratosis congenita (DC) is a rare inherited syndrome characterized by classical mucocutaneous features and the presence of other clinical features including bone marrow failure, pulmonary fibrosis, liver cirrhosis, and a predisposition to cancer. The symptoms develop at various ages and may manifest over time. Gene mutations associated with DC, such as DC1, TERC, TERT, TINF2, NHP2, NOP10, ACD, CTC1, NAF1, PARN, POT1, RTEL1, STN1, and WRAP53, have been identified in about 70% of patients. Read More

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https://www.karger.com/Article/FullText/494421
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http://dx.doi.org/10.1159/000494421DOI Listing
November 2018
7 Reads
0.994 Impact Factor

hnRNPA2 mediated acetylation reduces telomere length in response to mitochondrial dysfunction.

PLoS One 2018 14;13(11):e0206897. Epub 2018 Nov 14.

Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.

Telomeres protect against chromosomal damage. Accelerated telomere loss has been associated with premature aging syndromes such as Werner's syndrome and Dyskeratosis Congenita, while, progressive telomere loss activates a DNA damage response leading to chromosomal instability, typically observed in cancer cells and senescent cells. Therefore, identifying mechanisms of telomere length maintenance is critical for understanding human pathologies. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206897PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6241121PMC
November 2018
17 Reads
3.234 Impact Factor

Unrelated allogeneic hematopoietic stem cell transplantation in a patient with Revesz syndrome, a severe variant of dyskeratosis congenita.

Pediatr Blood Cancer 2019 Jan 26;66(1):e27476. Epub 2018 Sep 26.

Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.

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http://doi.wiley.com/10.1002/pbc.27476
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http://dx.doi.org/10.1002/pbc.27476DOI Listing
January 2019
1 Read

The Telomerase Complex Directly Controls Hematopoietic Stem Cell Differentiation and Senescence in an Induced Pluripotent Stem Cell Model of Telomeropathy.

Front Genet 2018 29;9:345. Epub 2018 Aug 29.

Cellular and Molecular Immunoregulation Group, Center for Translational Medicine, International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czechia.

Telomeropathies are rare disorders associated with impaired telomere length control mechanisms that frequently result from genetic mutations in the telomerase complex. Dyskeratosis congenita is a congenital progressive telomeropathy in which mutation in the telomerase RNA component () impairs telomere maintenance leading to accelerated cellular senescence and clinical outcomes resembling premature aging. The most severe clinical feature is perturbed hematopoiesis and bone-marrow failure, but the underlying mechanisms are not fully understood. Read More

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http://dx.doi.org/10.3389/fgene.2018.00345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123533PMC
August 2018
2 Reads

Landscape of the complete RNA chemical modifications in the human 80S ribosome.

Nucleic Acids Res 2018 Oct;46(18):9289-9298

Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Minami-osawa 1-1, Hachioji-shi, Tokyo 192-0397, Japan.

During ribosome biogenesis, ribosomal RNAs acquire various chemical modifications that ensure the fidelity of translation, and dysregulation of the modification processes can cause proteome changes as observed in cancer and inherited human disorders. Here, we report the complete chemical modifications of all RNAs of the human 80S ribosome as determined with quantitative mass spectrometry. We assigned 228 sites with 14 different post-transcriptional modifications, most of which are located in functional regions of the ribosome. Read More

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https://academic.oup.com/nar/advance-article/doi/10.1093/nar
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http://dx.doi.org/10.1093/nar/gky811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182160PMC
October 2018
10 Reads

Generation of an Rtel1-CreERT2 knock-in mouse model for lineage tracing RTEL1+ stem cells during development.

Transgenic Res 2018 12 8;27(6):571-578. Epub 2018 Sep 8.

Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada.

Regulator of telomere length 1 (RTEL1) DNA helicase has been demonstrated to be essential for the maintenance of telomeres and genomic stability. This function of RTEL1 could be required for protecting stem cells from genomic mutations as suggested by its selective expression in stem cell-zones, as well as by RTEL1 mutations identified in Hoyeraal-Hreidarsson syndrome, a severe dyskeratosis congenita that targets primarily stem cell compartments. As a first step to establish a role of RTEL1 in stem cells, we generated an Rtel1 mouse allele in which a tamoxifen-inducible Cre (CreERT2) cDNA was specifically knocked into the Rtel1 genomic locus and controlled by the endogenous Rtel1 regulatory elements. Read More

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http://dx.doi.org/10.1007/s11248-018-0093-yDOI Listing
December 2018
2.322 Impact Factor

Late exudative retinopathy after laser treatment for retinopathy of prematurity in a child with dyskeratosis congenita.

J AAPOS 2018 Aug 29. Epub 2018 Aug 29.

Department of Ophthalmology, Northwell Health, Zucker-Hofstra School of Medicine, Great Neck, New York.

Exudative retinopathy may be a manifestation of a variety of isolated ocular or systemic diseases in children. We report the case of a teenager with dyskeratosis congenita who developed a unilateral late exudative retinopathy after having previous laser treatment for threshold retinopathy of prematurity as an infant. Read More

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http://dx.doi.org/10.1016/j.jaapos.2018.06.004DOI Listing

Understanding the evolving phenotype of vascular complications in telomere biology disorders.

Angiogenesis 2019 Feb 25;22(1):95-102. Epub 2018 Aug 25.

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, 6E456, Bethesda, MD, 20892-6772, USA.

Vascular complications such as bleeding due to gastrointestinal telangiectatic anomalies, pulmonary arteriovenous malformations, hepatopulmonary syndrome, and retinal vessel abnormalities are being reported in patients with telomere biology disorders (TBDs) more frequently than previously described. The international clinical care consortium of telomere-associated ailments and family support group Dyskeratosis Congenita Outreach, Inc. held a workshop on vascular abnormalities in the TBDs at the National Cancer Institute in October 2017. Read More

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http://dx.doi.org/10.1007/s10456-018-9640-7DOI Listing
February 2019
8 Reads

De Novo Mutations Activating Germline TP53 in an Inherited Bone-Marrow-Failure Syndrome.

Am J Hum Genet 2018 Sep 23;103(3):440-447. Epub 2018 Aug 23.

Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan. Electronic address:

Inherited bone-marrow-failure syndromes (IBMFSs) include heterogeneous genetic disorders characterized by bone-marrow failure, congenital anomalies, and an increased risk of malignancy. Many lines of evidence have suggested that p53 activation might be central to the pathogenesis of IBMFSs, including Diamond-Blackfan anemia (DBA) and dyskeratosis congenita (DC). However, the exact role of p53 activation in each clinical feature remains unknown. Read More

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http://dx.doi.org/10.1016/j.ajhg.2018.07.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128301PMC
September 2018
14 Reads
10.931 Impact Factor

Diagnostics of rare disorders: whole-exome sequencing deciphering locus heterogeneity in telomere biology disorders.

Orphanet J Rare Dis 2018 Aug 17;13(1):139. Epub 2018 Aug 17.

Rare Disease Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: The telomere biology disorders (TBDs) include a range of multisystem diseases characterized by mucocutaneous symptoms and bone marrow failure. In dyskeratosis congenita (DKC), the clinical features of TBDs stem from the depletion of crucial stem cell populations in highly proliferative tissues, resulting from abnormal telomerase function. Due to the wide spectrum of clinical presentations and lack of a conclusive laboratory test it may be challenging to reach a clinical diagnosis, especially if patients lack the pathognomonic clinical features of TBDs. Read More

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http://dx.doi.org/10.1186/s13023-018-0864-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097299PMC
August 2018
2 Reads

Distinct pattern of neostriatal calcifications in dyskeratosis congenita: A case report and literature review.

Clin Neuropathol 2018 Nov/Dec;37(6):277-282

Dyskeratosis congenita (DKC) is a rare, inherited disorder classically known by the triad of nail dystrophy, mucosal leukoplakia, and lacy reticulated skin hyperpigmentation. Bone marrow failure is a prominent feature and accounts for most deaths in these patients. Genetic mutations resulting in shortened telomeres have been shown to cause DKC, which is the basis for categorizing it as a "premature aging syndrome". Read More

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http://dx.doi.org/10.5414/NP301088DOI Listing
February 2019
3 Reads

Homozygous OB-fold variants in telomere protein TPP1 are associated with dyskeratosis congenita-like phenotypes.

Blood 2018 Sep 31;132(12):1349-1353. Epub 2018 Jul 31.

Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.

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http://dx.doi.org/10.1182/blood-2018-03-837799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293869PMC
September 2018
4 Reads
10.452 Impact Factor

Evaluation and Management of Hematopoietic Failure in Dyskeratosis Congenita.

Authors:
Suneet Agarwal

Hematol Oncol Clin North Am 2018 Aug 28;32(4):669-685. Epub 2018 May 28.

Division of Hematology/Oncology, Harvard Medical School, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston Children's Hospital, 1 Blackfan Circle, Karp 07214, Boston, MA 02115, USA. Electronic address:

Dyskeratosis congenita (DC) is a rare, inherited bone marrow failure (BMF) syndrome characterized by variable manifestations and ages of onset, and predisposition to cancer. DC is one of a spectrum of diseases caused by mutations in genes regulating telomere maintenance, collectively referred to as telomere biology disorders (TBDs). Hematologic disease is common in children with DC/TBD. Read More

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http://dx.doi.org/10.1016/j.hoc.2018.04.003DOI Listing
August 2018
6 Reads

Outcome of haematopoietic stem cell transplantation in dyskeratosis congenita.

Br J Haematol 2018 Oct 9;183(1):110-118. Epub 2018 Jul 9.

Haematology Unit, Istituto Giannina Gaslini, Genoa, Italy.

Dyskeratosis congenita (DC) is a genetic multisystem disorder with frequent involvement of the bone marrow. Haematopoietic stem cell transplantation (HSCT) is the only definitive cure to restore haematopoiesis, even though it cannot correct other organ dysfunctions. We collected data on the outcome of HSCT in the largest cohort of DC (n = 94) patients ever studied. Read More

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http://dx.doi.org/10.1111/bjh.15495DOI Listing
October 2018
13 Reads

Reconsidering the indication of haematopoietic stem cell transplantation for dyskeratosis congenita.

Br J Haematol 2018 Oct 5;183(1):11-12. Epub 2018 Jul 5.

Paediatric Haematology and Oncology, Greifswald University Hospital, Greifswald, Germany.

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http://dx.doi.org/10.1111/bjh.15493DOI Listing
October 2018
2 Reads

[Inherited bone marrow failure syndrome: management and diagnostic advances utilizing next-generation sequencing].

Authors:
Hideki Muramatsu

Rinsho Ketsueki 2018 ;59(6):716-722

Department of Pediatrics, Nagoya University Graduate School of Medicine.

Inherited bone marrow failure syndromes (IBMFS) are part of a heterogeneous disease category in which at least one hematopoietic cell lineage is reduced in the bone marrow owing to a pathogenic genetic mutation. IBMFS comprise >25 defined disease entities, including Fanconi anemia (FA), Diamond-Blackfan anemia, and dyskeratosis congenita. The diagnosis is based on hematological and physical findings with the aid of several disease-specific diagnostic tests, such as the chromosomal breakage test for FA. Read More

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http://dx.doi.org/10.11406/rinketsu.59.716DOI Listing
January 2018
16 Reads

HuR regulates telomerase activity through TERC methylation.

Nat Commun 2018 06 7;9(1):2213. Epub 2018 Jun 7.

Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.

Telomerase consists of the catalytic protein TERT and the RNA TERC. Mutations in TERC are linked to human diseases, but the underlying mechanisms are poorly understood. Here we report that the RNA-binding protein HuR associates with TERC and promotes the assembly of the TERC/TERT complex by facilitating TERC C106 methylation. Read More

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http://dx.doi.org/10.1038/s41467-018-04617-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992219PMC
June 2018
11 Reads

Turning Uridines around: Role of rRNA Pseudouridylation in Ribosome Biogenesis and Ribosomal Function.

Biomolecules 2018 06 5;8(2). Epub 2018 Jun 5.

Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.

Ribosomal RNA (rRNA) is extensively edited through base methylation and acetylation, 2'-O-ribose methylation and uridine isomerization. In human rRNA, 95 uridines are predicted to by modified to pseudouridine by ribonucleoprotein complexes sharing four core proteins and differing for a RNA sequence guiding the complex to specific residues to be modified. Most pseudouridylation sites are placed within functionally important ribosomal domains and can influence ribosomal functional features. Read More

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http://dx.doi.org/10.3390/biom8020038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023024PMC
June 2018
1 Read

A call to study orphan diseases.

Authors:
Faizan Alawi

Oral Surg Oral Med Oral Pathol Oral Radiol 2018 08 22;126(2):95-97. Epub 2018 May 22.

Associate Professor of Pathology, University of Pennsylvania, School of Dental Medicine, 240 South 40th Street, Room 328B, Philadelphia, PA 19104, USA.

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https://linkinghub.elsevier.com/retrieve/pii/S22124403183093
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http://dx.doi.org/10.1016/j.oooo.2018.05.003DOI Listing
August 2018
2 Reads

Similar telomere attrition rates in androgen-treated and untreated patients with dyskeratosis congenita.

Blood Adv 2018 06;2(11):1243-1249

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

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome and the prototypic telomere biology disorder (TBD). Leukocyte telomere length (TL) less than the first percentile for age, measured by flow cytometry with in situ hybridization (flow FISH), is diagnostic of DC. Androgens are a therapeutic option for DC/TBD-associated bone marrow failure (BMF). Read More

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http://dx.doi.org/10.1182/bloodadvances.2018016964DOI Listing
June 2018
2 Reads

Potentially Malignant Oral Disorders and Cancer Transformation.

Anticancer Res 2018 Jun;38(6):3223-3229

Department of Oral Medicine and Pathology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Cancer in the oral cavity is often preceded by precursor lesions. Nine oral mucosal disorders are known to have an increased risk of malignant transformation. The etiology varies from disorders caused by exogenous factors such as tobacco and autoimmune inflammation to idiopathic or inherited genetic aberrations. Read More

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http://dx.doi.org/10.21873/anticanres.12587DOI Listing
June 2018
3 Reads

Dyskeratosis congenita with a novel genetic variant in the DKC1 gene: a case report.

BMC Med Genet 2018 05 25;19(1):85. Epub 2018 May 25.

Human Genetics Unit, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo 8, Sri Lanka.

Background: Dyskeratosis congenita (DC) is a rare genetic disorder of bone marrow failure inherited in an X-linked, autosomal dominant or autosomal recessive pattern. It has a wide array of clinical features and patients may be cared for by many medical sub specialties. The typical clinical features consist of lacy reticular skin pigmentation, nail dystrophy and oral leukoplakia. Read More

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http://dx.doi.org/10.1186/s12881-018-0584-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970516PMC
May 2018
11 Reads
2.083 Impact Factor

Beginning at the ends: telomeres and human disease.

Authors:
Sharon A Savage

F1000Res 2018 1;7. Epub 2018 May 1.

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

Studies of rare and common illnesses have led to remarkable progress in the understanding of the role of telomeres (nucleoprotein complexes at chromosome ends essential for chromosomal integrity) in human disease. Telomere biology disorders encompass a growing spectrum of conditions caused by rare pathogenic germline variants in genes encoding essential aspects of telomere function. Dyskeratosis congenita, a disorder at the severe end of this spectrum, typically presents in childhood with the classic triad of abnormal skin pigmentation, nail dystrophy, and oral leukoplakia, accompanied by a very high risk of bone marrow failure, cancer, pulmonary fibrosis, and other medical problems. Read More

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http://dx.doi.org/10.12688/f1000research.14068.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931273PMC
May 2018
1 Read

Recurrent somatic mutations are rare in patients with cryptic dyskeratosis congenita.

Leukemia 2018 Aug 2;32(8):1762-1767. Epub 2018 Apr 2.

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

Dyskeratosis congenita (DKC) is a paradigmatic telomere disorder characterized by substantial and premature telomere shortening, bone marrow failure, and a dramatically increased risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). DKC can occur as a late-onset, so-called cryptic form, with first manifestation in adults. Somatic MDS-related mutations are found in up to 35% of patients with acquired aplastic anemia (AA), especially in patients with short telomeres. Read More

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http://www.nature.com/articles/s41375-018-0125-x
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http://dx.doi.org/10.1038/s41375-018-0125-xDOI Listing
August 2018
21 Reads

A case report of heterozygous TINF2 gene mutation associated with pulmonary fibrosis in a patient with dyskeratosis congenita.

Medicine (Baltimore) 2018 May;97(19):e0724

Department of Respiratory Medicine, The First Affiliated Hospital, Sun Yat-sen University.

Rationale: Dyskeratosis congenita (DC) is a rare inherited disease characterized by the classical mucocutaneous triad. Pulmonary fibrosis, bone marrow failure, and solid tumors are the main causes of mortality in DC. Pathogenic variants in TERT, TERC, and DKC1 have been identified in individuals with familial pulmonary fibrosis. Read More

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http://dx.doi.org/10.1097/MD.0000000000010724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959423PMC
May 2018
14 Reads

The Guardian of the Genome Revisited: p53 Downregulates Genes Required for Telomere Maintenance, DNA Repair, and Centromere Structure.

Cancers (Basel) 2018 May 6;10(5). Epub 2018 May 6.

Genetics of Tumour Suppression, Equipe Labellisée Ligue, Institut Curie, Centre de recherche, 26 rue d'Ulm, 75248 Paris Cedex 05, France.

The p53 protein has been extensively studied for its capacity to prevent proliferation of cells with a damaged genome. Surprisingly, however, our recent analysis of mice expressing a hyperactive mutant p53 that lacks the C-terminal domain revealed that increased p53 activity may alter genome maintenance. We showed that p53 downregulates genes essential for telomere metabolism, DNA repair, and centromere structure and that a sustained p53 activity leads to phenotypic traits associated with dyskeratosis congenita and Fanconi anemia. Read More

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http://dx.doi.org/10.3390/cancers10050135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977108PMC
May 2018
8 Reads

A regulatory loop connecting WNT signaling and telomere capping: possible therapeutic implications for dyskeratosis congenita.

Ann N Y Acad Sci 2018 Apr;1418(1):56-68

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

The consequences of telomere dysfunction are most apparent in rare inherited syndromes caused by genetic deficiencies in factors that normally maintain telomeres. The principal disease is known as dyskeratosis congenita (DC), but other syndromes with similar underlying genetic defects share some clinical aspects with this disease. Currently, there are no curative therapies for these diseases of telomere dysfunction. Read More

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http://dx.doi.org/10.1111/nyas.13692DOI Listing
April 2018
2 Reads

Whole exome sequencing reveals rare variants linked to congenital pouch colon.

Sci Rep 2018 Apr 27;8(1):6646. Epub 2018 Apr 27.

Department of Biotechnology and Bioinformatics, Birla Institute of Scientific Research, Jaipur, 302001 RJ, India.

We demonstrate the application of whole exome sequencing to discover the rare variants for congenital pouch colon, acronymed CPC. For 18 affected individuals in a total of 64 samples, we sequenced coding regions to a mean coverage of 100×. A sufficient depth of ca. Read More

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http://dx.doi.org/10.1038/s41598-018-24967-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923232PMC

Refining the phenotype associated with biallelic DNAJC21 mutations.

Clin Genet 2018 Aug 7;94(2):252-258. Epub 2018 Jun 7.

Service de Génétique Médicale, CHU Sainte-Justine, Montréal, Canada.

Inherited bone marrow failure syndromes (IBMFS) are caused by mutations in genes involved in genomic stability. Although they may be recognized by the association of typical clinical features, variable penetrance and expressivity are common, and clinical diagnosis is often challenging. DNAJC21, which is involved in ribosome biogenesis, was recently linked to bone marrow failure. Read More

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http://dx.doi.org/10.1111/cge.13370DOI Listing
August 2018
4 Reads

Complex phenotype of dyskeratosis congenita and mood dysregulation with novel homozygous RTEL1 and TPH1 variants.

Am J Med Genet A 2018 06 25;176(6):1432-1437. Epub 2018 Apr 25.

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health, Rockville, Maryland.

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome caused by germline mutations in telomere biology genes. Patients have extremely short telomeres for their age and a complex phenotype including oral leukoplakia, abnormal skin pigmentation, and dysplastic nails in addition to bone marrow failure, pulmonary fibrosis, stenosis of the esophagus, lacrimal ducts and urethra, developmental anomalies, and high risk of cancer. We evaluated a patient with features of DC, mood dysregulation, diabetes, and lack of pubertal development. Read More

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http://dx.doi.org/10.1002/ajmg.a.38706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992073PMC
June 2018
30 Reads

Clinical features and presentation of oral potentially malignant disorders.

Oral Surg Oral Med Oral Pathol Oral Radiol 2018 06 4;125(6):582-590. Epub 2018 Apr 4.

Emeritus Professor, King's College London, UK; WHO Collaborating Centre for Oral Cancer, London, UK. Electronic address:

Oral potentially malignant disorders (OPMDs) are conditions that precede the onset of invasive cancers of the oral cavity. The term embraces precancerous lesions and conditions referred to in earlier World Health Organization (WHO) definitions. Leukoplakia is the most common OPMD; erythroplakia, although rare, is more serious. Read More

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http://dx.doi.org/10.1016/j.oooo.2018.03.011DOI Listing
June 2018
2 Reads

The C-Terminal Extension Unique to the Long Isoform of the Shelterin Component TIN2 Enhances Its Interaction with TRF2 in a Phosphorylation- and Dyskeratosis Congenita Cluster-Dependent Fashion.

Mol Cell Biol 2018 Jun 29;38(12). Epub 2018 May 29.

Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, USA

TIN2 is central to the shelterin complex, linking the telomeric proteins TRF1 and TRF2 with TPP1/POT1. Mutations in , which encodes TIN2, that are found in dyskeratosis congenita (DC) result in very short telomeres and cluster in a region shared by the two TIN2 isoforms, TIN2S (short) and TIN2L (long). Here we show that TIN2L, but not TIN2S, is phosphorylated. Read More

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http://dx.doi.org/10.1128/MCB.00025-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974431PMC
June 2018
7 Reads
4.780 Impact Factor

The age of heterozygous mutant parents influences the adult phenotype of their offspring irrespective of genotype in zebrafish.

Wellcome Open Res 2017 4;2:77. Epub 2017 Sep 4.

Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, UK.

Background: Mutations in proteins involved in telomere maintenance lead to a range of human diseases, including dyskeratosis congenita, idiopathic pulmonary fibrosis and cancer. Telomerase functions to add telomeric repeats back onto the ends of chromosomes, however non-canonical roles of components of telomerase have recently been suggested.

Methods: Here we use a zebrafish telomerase mutant which harbours a nonsense mutation in to investigate the adult phenotypes of fish derived from heterozygous parents of different ages. Read More

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http://dx.doi.org/10.12688/wellcomeopenres.12530.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840683PMC
September 2017
6 Reads

The role of telomere binding molecules for normal and abnormal hematopoiesis.

Int J Hematol 2018 Jun 17;107(6):646-655. Epub 2018 Mar 17.

Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

In order to maintain the homeostasis of the hematopoietic system, hematopoietic stem cells (HSCs) need to be maintained while slowly dividing over their lifetime. However, repeated cell divisions lead to the gradual accumulation of DNA damage and ultimately impair HSC function. Since telomeres are particularly fragile when subjected to replication stress, cells have several defense machinery to protect telomeres. Read More

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http://link.springer.com/10.1007/s12185-018-2432-4
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http://dx.doi.org/10.1007/s12185-018-2432-4DOI Listing
June 2018
8 Reads

Retinopathy and bone marrow failure revealing Coats plus syndrome.

BMJ Case Rep 2018 Mar 9;2018. Epub 2018 Mar 9.

Paediatric Haematology Department, Hospital Dona Estefania, CHLC, Lisbon, Portugal.

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http://dx.doi.org/10.1136/bcr-2018-224477DOI Listing
March 2018
2 Reads

Human RTEL1 stabilizes long G-overhangs allowing telomerase-dependent over-extension.

Nucleic Acids Res 2018 May;46(9):4533-4545

Institut Curie, PSL Research University, Sorbonne Universités, CNRS UMR3244 Telomere and cancer lab, 75005 Paris, France.

Telomere maintenance protects the cell against genome instability and senescence. Accelerated telomere attrition is a characteristic of premature aging syndromes including Dyskeratosis congenita (DC). Mutations in hRTEL1 are associated with a severe form of DC called Hoyeraal-Hreidarsson syndrome (HHS). Read More

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http://dx.doi.org/10.1093/nar/gky173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5961080PMC
May 2018
6 Reads

A unique homozygous WRAP53 Arg298Trp mutation underlies dyskeratosis congenita in a Chinese Han family.

BMC Med Genet 2018 03 7;19(1):40. Epub 2018 Mar 7.

State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China.

Background: Dyskeratosis congenita (DC) is an inherited telomeropathy characterized by mucocutaneous dysplasia, bone marrow failure, cancer predisposition, and other somatic abnormalities. Cells from patients with DC exhibit short telomere. The genetic basis of the majority of DC cases remains unknown. Read More

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http://dx.doi.org/10.1186/s12881-018-0549-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842585PMC
March 2018
1 Read

Novel variants in Nordic patients referred for genetic testing of telomere-related disorders.

Eur J Hum Genet 2018 06 26;26(6):858-867. Epub 2018 Feb 26.

Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.

Telomere-related disorders are a clinically and genetically heterogeneous group of disorders characterized by premature telomere shortening and proliferative failure of a variety of tissues. This study reports the spectrum of telomere-related gene variants and telomere length in Nordic patients referred for genetic testing due to suspected telomere-related disorder. We performed Sanger sequencing of the genes TERT, TERC, DKC1, and TINF2 on 135 unrelated index patients and measured telomere length by qPCR on DNA from peripheral blood leukocytes. Read More

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http://dx.doi.org/10.1038/s41431-018-0112-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974393PMC
June 2018
9 Reads