1,661 results match your criteria Dyskeratosis Congenita
Pathol Oncol Res 2018 Nov 27. Epub 2018 Nov 27.
Department of Pathology, NCI, Cairo University, Giza, Egypt.
The precise typing of precursor lesions of squamous cell carcinoma of vocal cord is of vital importance since it determines the line of therapy and prognosis. The aim of the present study is to evaluate the possible value of the types of dyskeratosis, histometry and cell proliferation rate in discriminating these lesions. The present retrospective study was based on 145 patients, classified according to the updated 2017 WHO system and included: Low-grade dysplasia (24 cases), high -grade dysplasia (53 cases), carcinoma insitu (33 cases) and microinvasive carcinomas (35 cases). Read More
Pediatr Blood Cancer 2018 Nov 26:e27557. Epub 2018 Nov 26.
Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Acta Haematol 2018 Nov 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
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
Histopathology 2018 Nov 8. Epub 2018 Nov 8.
Department of Dermatology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Aims: Persistent pruritic eruptions (PPEs), presenting with dyskeratotic keratinocytes histologically, are common in patients with adult-onset Still's disease (AOSD). The lesions may be histologically similar to other entities that present with dyskeratosis.
Methods And Results: To investigate whether histopathological findings can be used to discriminate among PPEs and other entities presenting with dyskeratotic keratinocytes, cutaneous histopathological changes of PPEs associated with AOSD (n=26) were compared with those of systemic lupus erythematosus (SLE) (n=16), dermatomyositis (n=19), and drug eruption (n=16). Read More
J Biol Chem 2018 Dec 5;293(49):18864-18878. Epub 2018 Oct 5.
From the Institute of Molecular and Cell Biology, A*STAR, Proteos, Singapore 138673,
The inflammasome is a critical molecular complex that activates interleukin-1 driven inflammation in response to pathogen- and danger-associated signals. Germline mutations in the inflammasome sensor NLRP1 cause Mendelian systemic autoimmunity and skin cancer susceptibility, but its endogenous regulation remains less understood. Here we use a proteomics screen to uncover dipeptidyl dipeptidase DPP9 as a novel interacting partner with human NLRP1 and a related inflammasome regulator, CARD8. Read More
Biomolecules 2018 Sep 26;8(4). Epub 2018 Sep 26.
IGF, CNRS, INSERM, University of Montpellier, F-34094 Montpellier, France.
RNA-RNA interaction slowly emerges as a critical component for the smooth functioning of gene expression processes, in particular in translation where the central actor is an RNA powered molecular machine. Overall, ribosome dynamic results from sequential interactions between three main RNA species: ribosomal, transfer and messenger RNA (rRNA, tRNA and mRNA). In recent decades, special attention has been paid to the physical principles governing codon-anticodon pairing, whereas individual RNA positioning mostly relies on ribosomal RNA framework. Read More
Pediatr Blood Cancer 2019 Jan 26;66(1):e27476. Epub 2018 Sep 26.
Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
Laryngoscope 2018 Sep 19. Epub 2018 Sep 19.
Department of Endoscopy, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Objectives: The purpose of this study was to introduce a new narrow band imaging (NBI) endoscopic classification for the diagnosis of vocal cord leukoplakia.
Study Design: Case series.
Methods: From January 2010 to February 2018, a total of 120 cases of vocal cord leukoplakia were enrolled in this study. Read More
Mil Med 2018 Sep 12. Epub 2018 Sep 12.
Department of Dermatology, San Antonio Military Health System, 3551 Roger Brooke Drive, San Antonio, TX.
Pemphigus foliaceus (PF) is an autoimmune dermatologic disease that typically presents with painful, superficial blisters that evolve into scaling erosions in a seborrheic distribution. This case study intends to demonstrate that due to the relative scarcity of the disease and its distribution on the body, PF can easily be misdiagnosed. We present a 43-year-old African American male that presented to the dermatology clinic with an 18-month history of non-pruritic, violaceous, scaling patches and plaques most prominent on the malar cheeks, upper chest and upper back. Read More
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
Skinmed 2018 1;16(4):273-274. Epub 2018 Jul 1.
From the Departments of Dermatology, Venereology and Leprology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India.
A 21-year-old man presented with extensive asymptomatic comedones and inflammatory papulonodules that had been present for the previous 7 years. The lesions had first appeared on the upper part of the trunk, subsequently spreading to the face, arms, axillae, thighs, groin, and buttocks. Physical examination revealed numerous monomorphic discrete black papules with firm central keratotic plugs. Read More
J Cutan Pathol 2018 Sep 10. Epub 2018 Sep 10.
Department of Dermatology, University of California San Francisco, San Francisco, California.
Background: Acantholysis can be seen in multiple skin diseases. Adnexal acantholysis has been regarded as a feature distinguishing pemphigus vulgaris (PV) from acantholytic conditions.
Methods: A retrospective review of the histopathologic features of diseases with acantholysis including PV, pemphigus foliaceus (PF), Hailey-Hailey disease (HHD), Darier disease (DD), Grover disease, and pityriasis rubra pilaris (PRP) was performed. Read More
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
Transgenic Res 2018 Dec 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
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
Angiogenesis 2018 Aug 25. 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
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
Am J Dermatopathol 2018 Sep 17. Epub 2018 Sep 17.
Department of Dermatology, Venerology and Allergology, University Medical Center, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.
Necrolytic migratory erythema (NEM) is associated with glucagonoma, an endocrine malignancy of the pancreas. It is a rare and a likely underrecognized paraneoplastic dermatitis. A 38-year-old woman presented to our clinic with a 3-year history of reocurring pruritic skin rashes with increasing intensity. Read More
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
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
Cureus 2018 Jun 1;10(6):e2727. Epub 2018 Jun 1.
Dermatologist, San Diego Family Dermatology, National City, USA.
Pagetoid dyskeratosis is a benign incidental pathologic finding that has been reported in many distinct skin lesions on various locations of the body. A man who had pagetoid dyskeratosis within lesions of the penile shaft is described and similar cases of pagetoid dyskeratosis in lesions of the male genitalia are reviewed. The patient was a 26-year-old healthy man who developed several asymptomatic penile papules that were refractory to topical imiquimod 5% cream and cryotherapy. Read More
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.
Acta Dermatovenerol Croat 2017 Dec;25(4):31-311
Nicola di Meo, MD, Dermatology Department, University of Trieste, Ospedale Maggiore di Trieste, Piazza Ospedale 1, IV Piano Palazzina Infettivi, 34100 Trieste, Italy;
Dear Editor, Grover's disease, also known as transient acantholytic dermatosis, is an idiopathic and acquired pruritic eruption of small vesicles and erythematous papules, classically on the central chest. The pathogenesis is not clearly defined, although heat sweating and occlusion have been interpreted as predisposing factors. We describe a case of monolateral acantholytic eruption with blaschkoid distribution in a patient treated with an orthopedic bandage for a shoulder injury. Read More
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
Rev Esp Patol 2018 Jul - Sep;51(3):188-192. Epub 2018 May 26.
Pathology Unit, Medical and Surgical Sciences Department, University of Cantabria and IDIVAL Research Institute, Santander, Spain. Electronic address:
Taxanes are antineoplastic drugs that can cause dermatotoxicity which can mimic an intraepidermal carcinoma. A 65-year-old woman presented with a cutaneous eruption suggestive of a paraneoplastic syndrome. Imaging studies showed multiple peritoneal nodules and associated ascites. Read More
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
Br J Haematol 2018 Oct 5;183(1):11-12. Epub 2018 Jul 5.
Paediatric Haematology and Oncology, Greifswald University Hospital, Greifswald, Germany.
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
Br J Dermatol 2018 Oct 12;179(4):1001-1002. Epub 2018 Aug 12.
Department of Dermatology, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv, 64239, Israel.
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
Biomolecules 2018 Jun 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
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.
Blood Adv 2018 Jun;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
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
Cell 2018 Jun 24;174(1):218-230.e13. Epub 2018 May 24.
Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address:
Ribonucleoprotein enzymes require dynamic conformations of their RNA constituents for regulated catalysis. Human telomerase employs a non-coding RNA (hTR) with a bipartite arrangement of domains-a template-containing core and a distal three-way junction (CR4/5) that stimulates catalysis through unknown means. Here, we show that telomerase activity unexpectedly depends upon the holoenzyme protein TCAB1, which in turn controls conformation of CR4/5. Read More
BMC Med Genet 2018 May 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
Zhonghua Xue Ye Xue Za Zhi 2018 May;39(5):414-419
Anemia Therapeutic Center, Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China.
To evaluate the impact of the targeted next-generation sequencing (NGS) assay for difficult congenital anemias. Blood Disease Hospital Anemia Panel 2014 (BDHAP-2014) including 217 known genes of congenital anemias was developed. NGS and parental verification were performed for patients who were suspected diagnosed with congenital anaemia from August 2014 to July 2017. Read More
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
Ugeskr Laeger 2018 May;180(19)
Dyskeratosis follicularis (or Darier's disease) is a genetic skin disease with an autosomal dominant inheritance and a prevalence of 1:100,000-1:35,000. Mutations in the gene ATP2A2 encoding the Ca2+-ATPase SERCA2 in the endoplasmatic reticulum lead to acantholysis and dyskeratosis in the epidermis, nails and mucosal membranes with resultant brown-yellow coloured, often infested skin papules and nail changes. The newly established Danish database for genodermatoses is embarking on an extensive registration of all Danish patients with Darier's disease. Read More
Int J Gynecol Pathol 2018 May 10. Epub 2018 May 10.
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (J.C.W., C.P.C., M.R.N.) Stanford University Hospital, Palo Alto, California (E.Y.) Laboratory of Experimental Pathology, GIGA-Cancer, University of Liege, Liege, Belgium (M.H.) Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon, France (T.G., M.T.).
High-grade vulvar intraepithelial neoplasia, a precursor lesion to vulvar squamous cell carcinoma, is subdivided into 2 types, classic or usual vulvar intraepithelial neoplasia (CVIN) and differentiated vulvar intraepithelial neoplasia (DVIN). CVIN, which is a human papilloma virus (HPV)-dependent lesion, is typically distinguished from DVIN, a p53 mutation-dependent process, by its distinct histomorphologic and immunohistochemical characteristics. However, distinguishing between the 2 entities becomes challenging in cases of CVIN with superimposed inflammatory changes, especially lichen simplex chronicus (LSC). Read More
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
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
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
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
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
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
Am J Med Genet A 2018 Jun 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
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