1,337 results match your criteria: "Dyskeratosis Congenita"

"Crying in the Wilderness"-The Use of Web-Based Support in Telomere Biology Disorders: Thematic Analysis.

JMIR Form Res

December 2024

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.

Background: Web-based information and social support are commonly used in rare disease communities where geographic dispersion and limited provider expertise complicate in-person support. We examined web-based resource use among caregivers of individuals with telomere biology disorders (TBDs), which are rare genetic conditions with long diagnostic odysseys and uncertain prognoses including multiorgan system cancer risk.

Objective: This study explored internet-based information-seeking and social support practices and perspectives of patients with TBDs and their caregivers.

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Hoyeraal-Hreidarsson syndrome: a case report of dyskeratosis congenita with a novel PARN gene mutation.

Ann Med Surg (Lond)

December 2024

University of Health Sciences, Adana Faculty of Medicine, Adana City Education and Research Hospital, Department of Pediatric Hematology and Oncology, Adana, Turkey.

Introduction And Importance: Dyskeratosis congenita (DC) is a rare multisystem disorder primarily characterized by bone marrow failure due to telomere shortening. Typical clinical features include oral leukoplakia, skin hyperpigmentation, and nail dystrophy, along with an increased risk of malignancies. Hoyeraal-Hreidarsson syndrome (HH), a severe variant of DC, is associated with profound neurological and immunological complications, emphasizing the importance of early diagnosis and genetic evaluation to guide appropriate management.

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Telomeres protect the ends of chromosomes but shorten following cell division in the absence of telomerase activity. When telomeres become critically short or damaged, a DNA damage response is activated. Telomeres then become dysfunctional and trigger cellular senescence or death.

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A "rotating menu" of medical uncertainty for families affected by telomere biology disorders: A qualitative interview study.

SSM Qual Res Health

December 2024

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Background: Medical uncertainty may cause distress and challenge medical decision-making for patients with rare diseases and their caregivers. Few studies have examined the experience and management of medical uncertainty in rare disease and the dynamics of multiple medical uncertainty sources, issues, and management strategies.

Objective: We explored the experience and management of uncertainty in individuals with telomere biology disorders (TBDs), a set of rare cancer-prone bone marrow failure syndromes, and their caregivers.

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Induced pluripotent stem cells (iPSCs) have emerged as powerful tools for in vitro modeling of bone marrow failure (BMF) syndromes and hereditary conditions predisposing to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This review synthesizes recent advances in iPSC-based disease modeling for various inherited BMF/MDS disorders, including Fanconi anemia, dyskeratosis congenita, Diamond Blackfan anemia syndrome, Shwachman-Diamond syndrome, and severe congenital neutropenia as well as GATA2, RUNX1, ETV6, ANKRD26, SAMD9, SAMD9L, and ADH5/ALDH2 syndromes. Although the majority of these iPSC lines are derived from patient cells, some are generated by introducing patient-specific mutations into healthy iPSC backgrounds, offering complementary approaches to disease modeling.

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Inherited Telomere Biology Disorders: Pathophysiology, Clinical Presentation, Diagnostics, and Treatment.

Transfus Med Hemother

October 2024

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

Article Synopsis
  • Telomeres protect chromosome ends from damage and shorten with cell division, which can lead to aging-related issues like cell senescence or death when they become critically short.
  • Premature aging and severe health complications, such as bone marrow failure and pulmonary fibrosis, can occur due to disorders affecting telomere maintenance, known as telomere biology disorders (TBDs).
  • Recognizing congenital causes of bone marrow failure in about 10% of cases is crucial for accurate diagnosis and treatment, emphasizing the need for proper counseling and donor selection for stem cell transplants.
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Telomeres and immunodeficiencies.

Hum Immunol

November 2024

Department of Allergy, Asthma and Inflammation, 1st Pediatric Clinic University of Athens, Childrens' Hospital 'Agia Sophia', Athens, Greece. Electronic address:

Article Synopsis
  • The immune system relies on the growth and specialization of specific lymphocytes to function effectively.
  • Telomeres, protective structures at the ends of chromosomes, vary in length among different lymphocyte types and can shorten with age.
  • Certain immune disorders, like dyskeratosis congenita and ICF syndrome, are linked to abnormal telomere shortening and issues with DNA repair and recombination.
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Article Synopsis
  • Dyskeratosis congenita (DC) is an inherited bone marrow disease marked by oral leukoplakia, nail dystrophy, and reticular hyperpigmentation, primarily due to DKC1 gene defects affecting telomeres.
  • Malignant changes in oral leukoplakia to squamous cell carcinoma (SCC) are rare in DC, particularly in younger patients, with only 1.5% of cases developing skin SCC.
  • A reported case describes a 12-year-old girl with a familial RTEL1 gene mutation showing a severe form of DC, leading to multiple skin SCCs.
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Article Synopsis
  • Rare variations in the RTEL1 gene are linked to telomere biology disorders (TBDs), with biallelic variants leading to severe conditions like dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome in childhood.* -
  • A study of 44 individuals showed that those with biallelic RTEL1 variants had earlier diagnoses and poorer survival rates compared to those with heterozygous variants, indicating a major impact of genotype on health outcomes.* -
  • Out of 257 unique RTEL1 variants identified, many are classified as variants of uncertain significance, highlighting the need for further research to standardize variant classification and improve clinical management of TBDs.*
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Article Synopsis
  • - The RTEL1 gene is essential for maintaining telomeres and genomic stability, with germline mutations linked to serious conditions like Hoyeraal-Hreidarsson syndrome.
  • - This study applied various bioinformatics tools to analyze 1392 non-synonymous SNPs (nsSNPs) in the RTEL1 gene, narrowing them down to 11 that are particularly harmful to the protein's structure and function.
  • - Additionally, the research explored how certain mutations disrupt protein-DNA interactions and identified regulatory non-coding variants, setting the stage for future investigations into RTEL1 gene variants and their implications for treatment.
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Locally advanced rectal cancer in a young adult affected with dyskeratosis congenita (Zinsser-Cole-Engman syndrome): a case report.

Surg Case Rep

September 2024

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.

Article Synopsis
  • Dyskeratosis congenita (DKC) is a genetic disease characterized by skin pigmentation issues, nail problems, and leukoplakia, with around 8-10% of patients developing cancers, including colorectal cancer.
  • A case study involved a 25-year-old man with DKC who was diagnosed with locally advanced rectal cancer, receiving total neoadjuvant therapy (chemotherapy followed by chemoradiation), which initially reduced the tumor.
  • Despite a near-complete response, the patient experienced tumor regrowth five months later and underwent a total pelvic exenteration surgery, after which he has remained cancer-free for one year.
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Article Synopsis
  • Telomere biology disorders (TBD) are inherited conditions linked to short telomeres, with dyskeratosis congenita (DC) being a severe phenotype characterized by various physical symptoms.
  • A case study details a 2-year-old girl with specific symptoms (reticulated pigmentary changes and Terry's nails) who was found to have a TERT gene variant and short telomeres, but did not show the full range of TBD features.
  • The report emphasizes the need for awareness and diagnosis of TBD, even in patients who exhibit only mild or limited symptoms of classic DC.
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The gray boundaries of aberrant shortening of the cellular timekeepers' edges.

EMBO Mol Med

October 2024

Centro de Investigaciones Energéticas Medioambientales y Tecnológicas and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIEMAT/CIBERER), Advanced Therapies Unit, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD UAM), Madrid, Spain.

Telomeres are supramolecular structures that allow the DNA strand to fold back on itself and protect the linear chromosome end from being sensed as a double-strand DNA break. Telomeric conservation relies on mechanisms that replace terminal DNA sequences, and ensuring structural integrity. Telomere biology disorders (TBDs) are a heterogeneous group of low-prevalence pathologies defined by germline mutations in genes involved in telomere maintenance mechanisms (TMMs).

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The evolving genetic landscape of telomere biology disorder dyskeratosis congenita.

EMBO Mol Med

October 2024

Centre for Genomics and Child Health, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, Newark Street, London, E12AT, UK.

Article Synopsis
  • - Dyskeratosis congenita (DC) is a rare inherited condition that leads to bone marrow failure and is largely linked to mutations affecting telomere biology, with about 35% of cases having unidentified genetic causes.
  • - Research on a wide range of DC and 'DC-like' cases uncovered new pathogenic variants, including findings in the novel X-linked gene POLA1 and in known genes POT1 and ZCCHC8, enhancing the understanding of the genetic basis of these disorders.
  • - Functional studies indicated that the new variants in POLA1 and POT1 disrupt crucial protein interactions that are essential for telomere maintenance, while ZCCHC8 variants lead to inflammation in patients, thereby contributing to the understanding of
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Telomere biology disorders: from dyskeratosis congenita and beyond.

Postgrad Med J

November 2024

Department of Pediatric Hematology-Oncology & Autologous Hematopoietic Stem Cell Transplantation Unit, University Hospital of Heraklion & Laboratory of Blood Diseases and Childhood Cancer Biology, School of Medicine, University of Crete, Voutes, Heraklion, Crete, 71500, Greece.

Article Synopsis
  • - Defective telomerase function leads to genomic instability, resulting in telomere biology disorders (telomeropathies), which are characterized by variations in telomere length and related health issues.
  • - These disorders can cause multiple organ effects and exhibit a variety of symptoms even among family members, sometimes linking to previously unexplained diseases like pulmonary fibrosis and liver cirrhosis.
  • - Patients with telomere biology disorders have an increased risk of specific cancers and may experience heightened sensitivity to standard chemotherapy, highlighting the need for better awareness and a multidisciplinary management approach for these conditions.
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Article Synopsis
  • Dyskeratosis congenita is a rare genetic disorder affecting skin, nails, and oral mucosa, with uncommon retinal involvement.
  • A young male patient with recurrent infections was diagnosed with cytomegalovirus retinitis and subsequently found to have dyskeratosis congenita due to a mutation in the DKC1 gene.
  • The case highlights that cytomegalovirus retinitis can indicate serious immunodeficiency in patients with dyskeratosis congenita, necessitating thorough examination.
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Article Synopsis
  • * A literature review was conducted to develop a user-friendly diagnostic algorithm to help clinicians identify these disorders and determine appropriate genetic testing.
  • * The research included a comprehensive search of databases, resulting in 625 relevant articles that discuss the different diseases and contributed to forming a clear approach for provisional diagnosis based on specific clinical factors.
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Article Synopsis
  • - Multiple mucocutaneous diseases, including oral lichen planus and oral discoid lupus erythematosus, have oral lesions often mistakenly labeled as "pre-cancerous", leading to confusion about their actual cancer risk.
  • - The study aimed to connect the occurrence of squamous cell carcinoma in these diseases to the concept of "Marjolin ulcer", which refers to cancer developing in chronic wound areas.
  • - Findings suggest that rather than being inherently "pre-malignant," these diseases may lead to squamous cell carcinoma primarily in long-standing, scarred lesions, indicating a need for careful monitoring of chronic oral conditions.
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Article Synopsis
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Diseases with oral malignant potential: Need for change to inform research, policy, and practice.

J Oral Pathol Med

September 2024

Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, University of Melbourne, Parkville, Victoria, Australia.

Article Synopsis
  • The manuscript critiques the existing classification of oral potentially malignant disorders, arguing that labeling many cases as precancerous is misleading since most do not progress to oral cancer.
  • It calls for a reclassification system that better reflects the actual risk of malignancy and proposes new categories for different levels of risk, including Oral Precancerous Diseases and Systemic Conditions with Oral Malignant Potential.
  • The authors aim to improve diagnostic and management strategies, reducing overdiagnosis and the associated burden on patients, while providing practical examples for research and clinical application.
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Article Synopsis
  • A 6-year-old girl with growth and blood disorders was found to have a specific genetic mutation linked to a potential new hereditary bone marrow failure syndrome.
  • Whole-exome analysis identified a homozygous variant in a gene associated with the Ras-MAPK pathway, which is known to cause RASopathies—a group of genetic diseases with similar symptoms like growth delays and facial features.
  • The study suggests that this mutation may disrupt protein interactions, likely contributing to the girl's unique clinical symptoms, and proposes this gene as a promising candidate for further research into RASopathies.
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