1,194 results match your criteria Dyskeratosis Congenita

Silencing circular RNA-friend leukemia virus integration 1 restrained malignancy of CC cells and oxaliplatin resistance by disturbing dyskeratosis congenita 1.

Open Life Sci 2022 18;17(1):563-576. Epub 2022 May 18.

Department of Gastrointestinal Surgery, The First College of Clinical Medical Science, China Three Gorges University, Phase 3, Jiangshan Duojiao, Wujiagang District, Yichang City, Hubei, 443000, China.

Circular-RNA friend leukemia virus integration 1 (circ-FLI1; hsa_circ_0000370) is a noninvasive biomarker for the diagnosis of colon carcinoma (CC). Herein, we intended to investigate its functions and competing endogenous RNA (ceRNA) mechanisms in CC cells. In terms of expression status, circ-FLI1 was abnormally upregulated in CC patients' tumors and cells, paralleled with DKC1 upregulation and miR-197-3p downregulation. Read More

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Recent advances in hematopoietic cell transplantation for inherited bone marrow failure syndromes.

Int J Hematol 2022 Jul 28;116(1):16-27. Epub 2022 May 28.

Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Aichi Medical Center Nagoya First Hospital, Nagoya, Japan.

Inherited bone marrow failure syndromes (IBMFSs) are a group of rare genetic disorders characterized by bone marrow failure with unique phenotypes and predisposition to cancer. Classical IBMFSs primarily include Fanconi anemia with impaired DNA damage repair, dyskeratosis congenita with telomere maintenance dysfunction, and Diamond-Blackfan anemia with aberrant ribosomal protein biosynthesis. Recently, comprehensive genetic analyses have been implemented for the definitive diagnosis of classic IBMFSs, and advances in molecular genetics have led to the identification of novel disorders such as AMeD and MIRAGE syndromes. Read More

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Dyskerin Downregulation Can Induce ER Stress and Promote Autophagy via AKT-mTOR Signaling Deregulation.

Biomedicines 2022 May 8;10(5). Epub 2022 May 8.

Department of Biology, University of Naples Federico II, 80126 Naples, Italy.

Dyskerin is an evolutionarily conserved nucleolar protein implicated in a wide range of fundamental biological roles, including telomere maintenance and ribosome biogenesis. Germline mutations of , the human gene encoding dyskerin, cause the hereditary disorders known as X-linked dyskeratosis congenita (X-DC). Moreover, dyskerin is upregulated in several cancers. Read More

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Inherited bone marrow failure in the pediatric patient.

Blood 2022 May 23. Epub 2022 May 23.

Queen Mary University of London, London, United Kingdom.

The inherited bone marrow (BM) failure syndromes are a diverse group of disorders characterized by BM failure usually in association with one or more extra-hematopoietic abnormality. The BM failure, which can involve one or more cell lineages, often presents in the pediatric age group. Furthermore, some children initially labelled as having "idiopathic aplastic anemia" or "myelodysplasia" represent cryptic presentations of these syndromes. Read More

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Truncating TINF2 p.Tyr312Ter variant and inherited breast cancer susceptibility.

Fam Cancer 2022 May 20. Epub 2022 May 20.

Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit and Biocenter Oulu, NordLab Oulu, University of Oulu, 90220, Aapistie 5A, Oulu, Finland.

TINF2 is a critical subunit of the shelterin complex, which protects and maintains the length of telomeres. Pathogenic missense and truncating TINF2 mutations are causative for dyskeratosis congenita (DC), a rare, dominantly inherited bone marrow failure syndrome characterized by mucocutaneous abnormalities and cancer predisposition. Recent reports indicate that specific TINF2 truncating mutations act as high penetrance cancer predisposition alleles outside DC context, including breast cancer in their tumor spectrum. Read More

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GSK3 inhibition rescues growth and telomere dysfunction in dyskeratosis congenita iPSC-derived type II alveolar epithelial cells.

Elife 2022 May 13;11. Epub 2022 May 13.

Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, United States.

Dyskeratosis congenita (DC) is a rare genetic disorder characterized by deficiencies in telomere maintenance leading to very short telomeres and the premature onset of certain age-related diseases, including pulmonary fibrosis (PF). PF is thought to derive from epithelial failure, particularly that of type II alveolar epithelial (AT2) cells, which are highly dependent on Wnt signaling during development and adult regeneration. We use human induced pluripotent stem cell-derived AT2 (iAT2) cells to model how short telomeres affect AT2 cells. Read More

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Genetics and genomics of bone marrow failure syndrome.

Blood Res 2022 Apr;57(S1):86-92

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Inherited bone marrow failure syndrome (IBMFS) is a group of clinically heterogeneous disorders characterized by significant hematological cytopenias of one or more hematopoietic cell lineages and is associated with an increased risk of cancer. The genetic etiology of IBMFS includes germline mutations impacting several key biological processes, such as DNA repair, telomere biology, and ribosome biogenesis, which may cause four major syndromes: Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome. Although the clinical features of some patients may be typical of a particular IBMFS, overlapping and atypical clinical manifestations and variable penetrance pose diagnostic challenges. Read More

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Are Dyskeratosis Congenita patients at higher risk of symptomatic COVID-19?

Med Hypotheses 2022 Jun 15;163:110843. Epub 2022 Apr 15.

Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.

Dyskeratosis Congenita (DC) is a rare and heterogeneous disease. This disorder is resulted from a defect in the telomere maintenance in stem cells. Telomerase RNA component, shelterin complex, and telomerase reverse transcriptase are mutated in this disease. Read More

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Case Report: Novel Biallelic Variants in Causing an Inherited Bone Marrow Failure Spectrum Phenotype: An Odyssey to Diagnosis.

Front Genet 2022 8;13:870233. Epub 2022 Apr 8.

Department of Genetics, Center of Genomic Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania.

Bone marrow failure represents an umbrella diagnosis for several life-threatening disorders. In many people, the etiology remains unknown for a long time, leading to an odyssey to diagnosis, with numerous tests performed and sometimes inappropriate treatment. Biallelic pathogenic variants in the gene were recently discovered to cause bone marrow failure syndrome type 3, having phenotypic overlap with Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, and Diamond-Blackfan anemia. Read More

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Case Report: A Missense Mutation in Dyskeratosis Congenita 1 Leads to a Benign Form of Dyskeratosis Congenita Syndrome With the Mucocutaneous Triad.

Front Pediatr 2022 6;10:834268. Epub 2022 Apr 6.

The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of China, Shanxi University, Taiyuan, China.

Background: Dyskeratosis congenita (DC) is a rare inheritable disorder characterized by bone marrow failure and mucocutaneous triad (reticular skin pigmentation, nail dystrophy, and oral leukoplakia). Dyskeratosis congenita 1 () is responsible for 4.6% of the DC with an X-linked inheritance pattern. Read More

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Sex differences in telomere length, lifespan, and embryonic dyskerin levels.

Peter M Lansdorp

Aging Cell 2022 05 20;21(5):e13614. Epub 2022 Apr 20.

Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, Canada.

Telomerase levels in most human cells are insufficient to prevent loss of telomeric DNA with each replication cycle. The resulting "Hayflick" limit may have allowed lifespan to increase by suppressing the development of tumors early in life be it at the expense of compromised cellular responses late in life. At any given age, the average telomere length in leukocytes shows considerably variation between individuals with females having, on average, longer telomeres than males. Read More

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Editing TINF2 as a potential therapeutic approach to restore telomere length in dyskeratosis congenita.

Blood 2022 04 14. Epub 2022 Apr 14.

Chan Zuckerberg Biohub, Innovative Genomics Institute, United States.

Mutations in the TINF2 gene, encoding the shelterin protein TIN2, cause telomere shortening and the inherited bone marrow failure syndrome dyskeratosis congenita (DC). A lack of suitable model systems limits the mechanistic understanding of telomere shortening in the stem cells and thus hinders the development of treatment options for bone marrow failure. Here, we endogenously introduced TIN2-DC mutations in human embryonic stem cells (hESCs) and human hematopoietic stem and progenitor cells (HSPCs) to dissect the disease mechanism and identified a gene editing strategy that rescued the disease phenotypes. Read More

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[Clinical features and advances in diagnoses and treatment of dyskeratosis congenita].

Z Q Yin Y Wan X F Zhu

Zhonghua Er Ke Za Zhi 2022 Apr;60(4):366-369

Pediatric Blood Diseases Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Tianjin 300020, China.

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Intron retention by a novel intronic mutation in DKC1 gene caused recurrent still birth and early death in a Chinese family.

Mol Genet Genomic Med 2022 06 6;10(6):e1934. Epub 2022 Apr 6.

Center of Molecular Medicine, Pediatrics Research Institute, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.

Background: DKC1, the dyskerin encoding gene, functions in telomerase activity and telomere maintenance. DKC1 mutations cause a multisystem disease, dyskeratosis congenita (DC), which is associated with immunodeficiency and bone marrow failure.

Methods: In this research, we reported a novel intronic mutation of DKC1 causing dyskerin functional loss in a Chinese family. Read More

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Multisystemic Manifestations in Rare Diseases: The Experience of Dyskeratosis Congenita.

Genes (Basel) 2022 03 11;13(3). Epub 2022 Mar 11.

Department of Pediatric Surgery, Meyer Children's Hospital, Viale Gaetano Pieraccini 24, 50139 Florence, Italy.

Dyskeratosis congenital (DC) is the first genetic syndrome described among telomeropathies. Its classical phenotype is characterized by the mucocutaneous triad of reticulated pigmentation of skin lace, nail dystrophy and oral leukoplakia. The clinical presentation, however, is heterogeneous and serious clinical complications include bone marrow failure, hematological and solid tumors. Read More

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Resonance assignment and secondary structure of the tandem harmonin homology domains of human RTEL1.

Biomol NMR Assign 2022 04 23;16(1):159-164. Epub 2022 Mar 23.

Molecular Biophysics Unit, Indian Institute of Science, Bengaluru, 560012, India.

Regulator of telomere elongation helicase 1 (RTEL1) is an Fe-S cluster containing DNA helicase that plays important roles in telomere DNA maintenance, DNA repair, and genomic stability. It is a modular protein comprising an N-terminal helicase domain, two tandem harmonin homology domains 1 & 2 (HHD1 and HHD2), and a C-terminal C4C4 type RING domain. The N-terminal helicase domain disassembles the telomere t/D-loop and unwinds the G-quadruplex via its helicase activity. Read More

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ERRATUM: Partial retraction of "Dyskeratosis congenita" [Autops Case Rep 10(3) (2020) e2020203].


Autops Case Rep 2022 11;12:e2021349. Epub 2022 Feb 11.

[This corrects the article DOI: 10.4322/acr.2021. Read More

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February 2022

Bilateral cytomegalovirus retinitis as the presenting feature of Dyskeratosis Congenita.

Eur J Ophthalmol 2022 Mar 4:11206721221086154. Epub 2022 Mar 4.

Advanced Eye Centre, 29751Post Graduate Institute of Medical Education and Research, Chandigarh-160012, India.

Purpose: To describe a young male with bilateral sequential Cytomegalovirus retinitis (CMVR) as the presenting feature of Dyskeratosis Congenita.

Case Report: A 25-year-old human immunodeficiency virus (HIV) negative male developed CMVR in his left eye, while on a three week course of oral valganciclovir therapy for CMV retinitis in his right eye. Systemic examination revealed reticular hypopigmentation of the forearms, dystrophic nails, oral leukoplakia and complete blood counts showed pancytopenia. Read More

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[Hoyeraal-Hreidarsson syndrome with combined immunodeficiency and enterocolitis caused by a DCK1 gene variant].

Zhonghua Er Ke Za Zhi 2022 Mar;60(3):248-249

Department of Pediatrics, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.

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A New Pathogenic Variant of the RTEL1 Gene and Dyskeratosis Congenita: A Dermatological View.

Acta Derm Venereol 2022 05 10;102:adv00710. Epub 2022 May 10.

Department of Dermatology and Allergy, Copenhagen University Hospital, Herlev and Gentofte, Gentofte Hospitalsvej 1, DK-2900 Hellerup, Denmark.

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Telomere biology disorders gain a family member.

Sharon A Savage

Blood 2022 02;139(7):957-959

National Cancer Institute.

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February 2022

Two Cases of Dyskeratosis Congenita with Clinically Distinct Presentations, Seen in National University Hospital, Singapore.

Skin Appendage Disord 2022 Jan 23;8(1):53-56. Epub 2021 Aug 23.

Department of Dermatology, National University Hospital, Singapore, Singapore.

Dyskeratosis congenita (DKC) is a genodermatosis of variable inheritance and is often characterised by the classical triad of nail dysplasia, reticulate hyperpigmentation of upper chest and neck, and oral leukoplakia. We report 2 cases of DKC from National University Hospital, Singapore, whose clinical presentations differed greatly from each other. Dermatologists should hold a high index of suspicion for DKC in young patients who present without the classical triad of features, as early dermatological care can be instituted through reinforcement of rigorous sun protection and regular surveillance for skin cancers. Read More

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January 2022

Molecular insight of dyskeratosis congenita: Defects in telomere length homeostasis.

J Clin Transl Res 2022 Feb 3;8(1):20-30. Epub 2022 Jan 3.

Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran.

Background: Dyskeratosis congenita (DC) is a rare disease and is a heterogenous disorder, with its inheritance patterns as autosomal dominant, autosomal recessive, and X-linked recessive. This disorder occurs due to faulty maintenance of telomeres in stem cells. This congenital condition is diagnosed with three symptoms: oral leukoplakia, nail dystrophy, and abnormal skin pigmentation. Read More

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February 2022

Inherited human Apollo deficiency causes severe bone marrow failure and developmental defects.

Blood 2022 04;139(16):2427-2440

Laboratory of Genome Dynamics in the Immune System, Laboratoire labellisé Ligue Naionale contre le Cancer, INSERM UMR 1163, Université de Paris, Imagine Institute, Paris, France.

Inherited bone marrow failure syndromes (IBMFSs) are a group of disorders typified by impaired production of 1 or several blood cell types. The telomere biology disorders dyskeratosis congenita (DC) and its severe variant, Høyeraal-Hreidarsson (HH) syndrome, are rare IBMFSs characterized by bone marrow failure, developmental defects, and various premature aging complications associated with critically short telomeres. We identified biallelic variants in the gene encoding the 5'-to-3' DNA exonuclease Apollo/SNM1B in 3 unrelated patients presenting with a DC/HH phenotype consisting of early-onset hypocellular bone marrow failure, B and NK lymphopenia, developmental anomalies, microcephaly, and/or intrauterine growth retardation. Read More

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Lipoprotein particle alterations due to androgen therapy in individuals with dyskeratosis congenita.

EBioMedicine 2022 Jan 17;75:103760. Epub 2021 Dec 17.

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

Background: Dyskeratosis congenita (DC) is a telomere biology disorder associated with high rates of bone marrow failure (BMF) and other medical complications. Oral androgens are successfully used to treat BMF in DC but often have significant side effects, including elevation of serum lipids. This study sought to determine the extent to which oral androgen therapy altered lipid and lipoprotein levels. Read More

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January 2022

Erratum: Partial retraction of "Dyskeratosis congenita" [Autops Case Rep 10(3) (2020) e2020203].


Autops Case Rep 2021 1;11:e2021341. Epub 2021 Nov 1.

[This corrects the article DOI: 10.4322/acr.2020. Read More

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November 2021

Biallelic TERT variant leads to Hoyeraal-Hreidarsson syndrome with additional dyskeratosis congenita findings.

Am J Med Genet A 2022 04 9;188(4):1226-1232. Epub 2021 Dec 9.

Institute of Health Sciences, Koç University, Istanbul, Turkey.

Short telomere syndromes constitute a heterogeneous group of clinical conditions characterized by short telomeres and impaired telomerase activity due to pathogenic variants in the essential telomerase components. Dyskeratosis congenita (DC) is a rare, multisystemic telomere biology disorder characterized by abnormal skin pigmentation, oral leukoplakia and nail dysplasia along with various somatic findings. Hoyeraal-Hreidarsson syndrome (HHS) is generally an autosomal recessively inherited subgroup showing growth retardation, microcephaly, cerebellar hypoplasia and severe immunodeficiency. Read More

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