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    912 results match your criteria Dyskeratosis Congenita

    1 OF 19

    The genomics of inherited bone marrow failure: from mechanism to the clinic.
    Br J Haematol 2017 Feb 17. Epub 2017 Feb 17.
    Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    The inherited bone marrow failure syndromes (IBMFS) typically present with significant cytopenias in at least one haematopoietic cell lineage that may progress to pancytopenia, and are associated with increased risk of cancer. Although the clinical features of the IBMFS are often diagnostic, variable disease penetrance and expressivity may result in diagnostic dilemmas. The discovery of the genetic aetiology of the IBMFS has been greatly facilitated by next-generation sequencing methods. Read More

    Structural Analysis Reveals the Deleterious Effects of Telomerase Mutations in Telomerase-Associated Bone Marrow Failure Syndromes.
    J Biol Chem 2017 Feb 1. Epub 2017 Feb 1.
    The Wistar Institute, United States;
    Naturally occurring mutations in the ribonucleoprotein reverse transcriptase, telomerase, are associated with the bone marrow failure syndromes dyskeratosis congenita (DKC), aplastic anemia (AA), and idiopathic pulmonary fibrosis (IPF). However, the mechanism by which these mutations impact telomerase function remains unknown. Here we present the structure of the human telomerase c-terminal extension (CTE or thumb domain) determined by the method of single-wavelength anomalous diffraction (SAD) to 2. Read More

    Defects in Lymphocyte Telomere Homeostasis Contribute to Cellular Immune phenotype in Cartilage-Hair Hypoplasia.
    J Allergy Clin Immunol 2017 Jan 23. Epub 2017 Jan 23.
    Section of Immunology, Allergy and Rheumatology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA. Electronic address:
    Background: Mutations in the lncRNA RNase component of the Mitochondrial RNA Processing endoribonuclease (RMRP) give rise to the autosomal recessive condition cartilage-hair hypoplasia (CHH). The CHH disease phenotype has some overlap with dyskeratosis congenita, a well known "telomere disorder". RMRP binds the telomerase reverse transcriptase protein TERT in some cell lines, raising the possibility that RMRP may play a role in telomere biology. Read More

    [Dangerous liaisons: p53, dyskeratosis congenita and Fanconi anemia].
    Med Sci (Paris) 2017 Jan 25;33(1):95-98. Epub 2017 Jan 25.
    Génétique de la suppression tumorale, Équipe Labellisée Ligue, Institut Curie, Centre de recherche, 26, rue d'Ulm, 75248 Paris Cedex 05, France - Sorbonne Universités, UPMC, Université Paris 6, Paris, France - CNRS UMR 3244, Paris, France - PSL Research University, Paris, France.

    Current Knowledge and Priorities for Future Research in Late Effects after Hematopoietic Cell Transplantation for Inherited Bone Marrow Failure Syndromes: Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation.
    Biol Blood Marrow Transplant 2017 Jan 20. Epub 2017 Jan 20.
    Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
    Fanconi anemia (FA), dyskeratosis congenita (DC), and Diamond Blackfan anemia (DBA) are 3 of the most common inherited bone marrow failure syndromes (IBMFS), in which the hematologic manifestations can be cured with hematopoietic cell transplantation (HCT). Later in life, these patients face a variety of medical conditions, which may be a manifestation of underlying disease or due to pre-HCT therapy, the HCT, or a combination of all these elements. Very limited long-term follow-up data exist in these populations, with FA the only IBMFS that has specific published data. Read More

    Life and Death of Yeast Telomerase RNA.
    J Mol Biol 2017 Jan 20. Epub 2017 Jan 20.
    Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Applied Cancer Research Pavillion, 3201 rue Jean-Mignault, Sherbrooke, Quebec, J1E 4K8, Canada. Electronic address:
    Telomerase reverse transcriptase elongates telomeres to overcome their natural attrition and allow unlimited cellular proliferation, a characteristic shared by stem cells and the majority of malignant cancerous cells. The telomerase holoenzyme comprises a core RNA molecule, a catalytic protein subunit, and other accessory proteins. Malfunction of certain telomerase components can cause serious genetic disorders including dyskeratosis congenita and aplastic anaemia. Read More

    Retinal findings and a novel TINF2 mutation in Revesz syndrome: Clinical and molecular correlations with pediatric retinal vasculopathies.
    Ophthalmic Genet 2017 Jan-Feb;38(1):51-60. Epub 2017 Jan 17.
    a Retina Service, Department of Ophthalmology , Massachusetts Eye and Ear, Harvard Medical School , Boston , Massachusetts , USA.
    Background: Revesz syndrome is a telomere disorder in the dyskeratosis congenita (DKC) spectrum characterized by exudative retinopathy, bone marrow failure, neuroradiographic abnormalities, and integumentary findings.

    Materials/methods: We report the ophthalmologic findings, documented by examinations under anesthesia with clinical photography and fluorescein angiography, as well as the systemic manifestations and genetic and molecular testing, in identical twins with Revesz syndrome, and compare and contrast these features to those of other pediatric retinal vasculopathies.

    Results: Both twins exhibited widespread avascularity and anomalous vasculature of the retinal periphery, retinal telangiectasias, and exudation. Read More

    Fatal Hemorrhagic Gastrointestinal Angioectasia after Bone Marrow Transplantation for Dyskeratosis Congenita.
    Intern Med 2016;55(23):3441-3444. Epub 2016 Dec 1.
    Department of Gastroenterology, Tokai University School of Medicine, Japan.
    Dyskeratosis congenita (DC) is a rare inherited disease in which the telomere complex cannot be maintained. Shortened telomeres can cause a number of clinical conditions. We herein report a case of unrelated bone marrow transplantation due to aplastic anemia associated with DC. Read More

    Diffuse Mesangial Sclerosis in a Child With Dyskeratosis Congenita Leading to End-stage Renal Disease.
    Iran J Kidney Dis 2016 Nov;10(6):416-418
    Nephropediatric Department, Charles Nicolle Hospital, Tunisia.
    Dyskeratosis congenita (DC) is a very rare inherited disorder. It is caused by dysfunction of telomere maintenance. It involves RNA telomerase components relevant to various mutations leading to a classic triad of physical findings consisting of nail dystrophy of the hands and feet, mucosal leukoplakia, and reticular pigmentation of the skin, most commonly on the head, neck, and trunk. Read More


    Investigation of chromosome X inactivation and clinical phenotypes in female carriers of DKC1 mutations.
    Am J Hematol 2016 Dec 4;91(12):1215-1220. Epub 2016 Nov 4.
    Molecular and Cellular Pharmacology Group, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
    Dyskeratosis congenita (DC) is an inherited bone marrow failure and cancer susceptibility syndrome caused by germline mutations in telomere biology genes. Germline mutations in DKC1, which encodes the protein dyskerin, cause X-linked recessive DC. Because of skewed X-chromosome inactivation, female DKC1 mutation carriers do not typically develop clinical features of DC. Read More

    Structural and functional consequences of a disease mutation in the telomere protein TPP1.
    Proc Natl Acad Sci U S A 2016 Nov 2;113(46):13021-13026. Epub 2016 Nov 2.
    Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109;
    Telomerase replicates chromosome ends to facilitate continued cell division. Mutations that compromise telomerase function result in stem cell failure diseases, such as dyskeratosis congenita (DC). One such mutation (K170Δ), residing in the telomerase-recruitment factor TPP1, provides an excellent opportunity to structurally, biochemically, and genetically dissect the mechanism of such diseases. Read More

    Clonal hematopoiesis in patients with dyskeratosis congenita.
    Am J Hematol 2016 Dec 21;91(12):1227-1233. Epub 2016 Oct 21.
    Comprehensive Bone Marrow Failure Center, Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104.
    Dyskeratosis congenita (DC) is a rare inherited telomeropathy most frequently caused by mutations in a number of genes all thought to be involved in telomere maintenance. The main causes of mortality in DC are bone marrow failure as well as malignancies including leukemias and solid tumors. The clinical picture including the degree of bone marrow failure is highly variable and factors that contribute to this variability are poorly understood. Read More

    Otologic manifestations of Fanconi anemia and other inherited bone marrow failure syndromes.
    Pediatr Blood Cancer 2016 Dec 18;63(12):2139-2145. Epub 2016 Jul 18.
    National Cancer Institute, National Institutes of Health, Rockville, Maryland.
    Background: The inherited bone marrow failure syndromes (IBMFSs) are diverse disorders with syndrome-specific features; their otologic and audiologic manifestations have not been well described. Our objective was to characterize these in patients with Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS), and to determine the association between physical findings and hearing loss.

    Methods: Patients with an IBMFS underwent comprehensive clinical and laboratory evaluations and testing for syndrome-specific gene mutations. Read More

    [(Pan-)cytopenia as first manifestation of kryptic telomeropathies in adults].
    Dtsch Med Wochenschr 2016 Oct 17;141(21):1578-1580. Epub 2016 Oct 17.
    Telomere syndromes (syn. Telomeropathies) are inherited disorders hallmarked by accelerated telomere shortening based on a molecular defect within the telomerase/telomere complex. The rare, but well-defined model disorder Dyskeratosis congenita (DKC) characterized by typical skin manifestations and bone marrow failure represents the classical manifestation of telomere syndromes in childhood and adolescence. Read More

    Allogeneic hematopoietic stem cell transplantation for dyskeratosis congenita.
    Curr Opin Hematol 2016 Nov;23(6):501-507
    Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
    Purpose Of Review: Dyskeratosis congenita is an inherited bone marrow failure syndrome caused by defects in telomere maintenance. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for bone marrow failure because of dyskeratosis congenita. The present review summarizes the literature with respect to the diagnosis and treatment of patients with dyskeratosis congenita who received HSCT, and discusses the recent progress in the management of dyskeratosis congenita. Read More

    RETINAL VASCULAR TORTUOSITY AND EXUDATIVE RETINOPATHY IN A FAMILY WITH DYSKERATOSIS CONGENITA MASQUERADING AS FAMILIAL EXUDATIVE VITREORETINOPATHY.
    Retin Cases Brief Rep 2017 Winter;11 Suppl 1:S187-S190
    *Associated Retinal Consultants, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan; †Department of Neurology and Ophthalmology, Michigan State University, East Lansing, Michigan; ‡Department of Ophthalmology, Beaumont Hospital-Southshore Campus, Trenton, Michigan; §Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts; ¶Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; and **Florida Retina Institute, Jacksonville, Florida.
    Purpose: To report a novel presentation of dyskeratosis congenita masquerading as familial exudative vitreoretinopathy.

    Methods: Observational case series involving single family and literature review.

    Results: A brother and sister were diagnosed with familial exudative vitreoretinopathy at ages 4 and 2, respectively. Read More

    Marked overlap of four genetic syndromes with dyskeratosis congenita confounds clinical diagnosis.
    Haematologica 2016 Oct 9;101(10):1180-1189. Epub 2016 Sep 9.
    Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Barts NHS Trust, London, UK.
    Dyskeratosis congenita is a highly pleotropic genetic disorder. This heterogeneity can lead to difficulties in making an accurate diagnosis and delays in appropriate management. The aim of this study was to determine the underlying genetic basis in patients presenting with features of dyskeratosis congenita and who were negative for mutations in the classical dyskeratosis congenita genes. Read More

    Dyskeratosis congenita presenting with dysphagia.
    Indian Dermatol Online J 2016 Jul-Aug;7(4):275-7
    Department of Dermatology, Venereology and Leprosy, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India.
    Dyskeratosiscongenita (DKC) is a genetically heterogeneous disease of defective telomere maintenance that may demonstrate different patterns of inheritance. It is characterized by thetriad of dystrophy of the nails, leukokeratosis of the oral mucosa, and extensive net-like pigmentation of the skin. We report a case ofDKC who presented with a chief complaint of dysphagia. Read More

    Enhancing a Wnt-Telomere Feedback Loop Restores Intestinal Stem Cell Function in a Human Organotypic Model of Dyskeratosis Congenita.
    Cell Stem Cell 2016 Sep 18;19(3):397-405. Epub 2016 Aug 18.
    Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Cell and Molecular Biology Program, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:
    Patients with dyskeratosis congenita (DC) suffer from stem cell failure in highly proliferative tissues, including the intestinal epithelium. Few therapeutic options exist for this disorder, and patients are treated primarily with bone marrow transplantation to restore hematopoietic function. Here, we generate isogenic DC patient and disease allele-corrected intestinal tissue using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated gene correction in induced pluripotent stem cells and directed differentiation. Read More

    Zinsser-Cole-Engman Syndrome: A Rare Case Report.
    J Clin Diagn Res 2016 Jun 1;10(6):ZD07-9. Epub 2016 Jun 1.
    Private practitioner, Karimnagar, Telangana, India .
    Zinsser-Cole-Engmann syndrome also called Dyskeratosis Congenita (DKC) is a rare genodermatosis first described by Zinsser in 1906. Mutations in DKC1 gene is responsible for DKC. It is usually inherited as an X-linked recessive trait, resulting in a striking male predilection. Read More

    Recent advances in inherited bone marrow failure syndrome research.
    Rinsho Ketsueki 2016 Jul;57(7):882-90
    Department of Pediatrics, Hirosaki University Graduate School of Medicine.
    Inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders characterized by bone marrow failure, congenital anomalies, and an increased risk of malignancies. Diagnosis is often difficult due to the wide variety of clinical expressions. The representative diseases are Diamond Blackfan anemia (DBA), Fanconi anemia (FA), congenital sideroblastic anemia (CSA), congenital dyserhthropoietic anemia, Shwachman Diamond syndrome, and dyskeratosis congenita. Read More

    The limitations of qPCR telomere length measurement in diagnosing dyskeratosis congenita.
    Mol Genet Genomic Med 2016 Jul 20;4(4):475-9. Epub 2016 Mar 20.
    Clinical Genetics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute, National Institutes of Health 9609 Medical Center Drive Rockville Maryland 20850.
    Background: Telomere length <1st percentile-for-age in leukocyte subsets by flow cytometry with fluorescence in situ hybridization (flow FISH) is highly sensitive and specific in diagnosing patients with dyskeratosis congenita (DC), a telomere biology disorder.

    Methods: We evaluated the clinical utility of the high-throughput quantitative real-time PCR (qPCR) relative telomere length (RTL) measurement as a diagnostic test for DC in patients with a priori clinical and/or genetic DC diagnoses. We calculated the sensitivity and specificity of RTL at different age-specific percentile cutoffs in 31 patients with DC and 51 mutation-negative relatives, and evaluated RTL difference by disease genotype. Read More

    Avascular Necrosis of Head of Femur in Dyskeratosis Congenita - A Rare Presentation.
    Indian J Hematol Blood Transfus 2016 Jun 7;32(Suppl 1):228-32. Epub 2015 Feb 7.
    Department of Orthopaedics, Indira Gandhi Medical College, Shimla, Himachal Pradesh India ; Prakash Niwas, Near Chitkara Park, Lower Kaithu, Shimla, 171003 India.
    Avascular necrosis of head of femur is a rare presentation in Dyskeratosis Congenita (DC). Aplastic anaemia, increased susceptibility to infections and fatal pulmonary complications often complicate the clinical scenario in these patients leading to short life span and difficulty in performing surgical interventions. The diagnosis initially and subsequent management by total hip replacement posed a great challenge. Read More

    Hypo- and Hyper-Assembly Diseases of RNA-Protein Complexes.
    Trends Mol Med 2016 Jul 3;22(7):615-28. Epub 2016 Jun 3.
    Department of Chemistry and Biochemistry, University of Colorado Boulder, Boulder, CO, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address:
    A key aspect of cellular function is the proper assembly and utilization of ribonucleoproteins (RNPs). Recent studies have shown that hyper- or hypo-assembly of various RNPs can lead to human diseases. Defects in the formation of RNPs lead to 'RNP hypo-assembly diseases', which can be caused by RNA degradation outcompeting RNP assembly. Read More

    Hereditary Predispositions to Myelodysplastic Syndrome.
    Int J Mol Sci 2016 May 30;17(6). Epub 2016 May 30.
    Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
    Myelodysplastic syndromes (MDS) are heterogeneous clonal hematopoietic disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. Familial forms of MDS have traditionally been considered rare, especially in adults; however, the increasing availability of somatic and germline genetic analyses has identified multiple susceptibility loci. Bone marrow failure syndromes have been well-described in the pediatric setting, e. Read More

    Rothmund-Thomson Syndrome: novel pathogenic mutations and frequencies of variants in the RECQL4 and USB1 (C16orf57) gene.
    Mol Genet Genomic Med 2016 May 24;4(3):359-66. Epub 2016 Feb 24.
    Division of Human GeneticsDepartment of PaediatricsInselspitalUniversity of BernCH-3010BernSwitzerland; Department of Clinical ResearchUniversity of BernCH-3010BernSwitzerland.
    Background: Poikiloderma is defined as a chronic skin condition presenting with a combination of punctate atrophy, areas of depigmentation, hyperpigmentation and telangiectasia. In a variety of hereditary syndromes such as Rothmund-Thomson syndrome (RTS), Clericuzio-type poikiloderma with neutropenia (PN) and Dyskeratosis Congenita (DC), poikiloderma occurs as one of the main symptoms. Here, we report on genotype and phenotype data of a cohort of 44 index patients with RTS or related genodermatoses. Read More

    Evaluation of Patients and Families With Concern for Predispositions to Hematologic Malignancies Within the Hereditary Hematologic Malignancy Clinic (HHMC).
    Clin Lymphoma Myeloma Leuk 2016 Jul 27;16(7):417-428.e2. Epub 2016 Apr 27.
    Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX.
    Introduction: Although multiple predispositions to hematologic malignancies exist, evaluations for hereditary cancer syndromes (HCS) are underperformed by most hematologist/oncologists. Criteria for initiating HCS evaluation are poorly defined, and results of genetic testing for hereditary hematologic malignancies have not been systematically reported.

    Patients And Methods: From April 2014 to August 2015, 67 patients were referred to the Hereditary Hematologic Malignancy Clinic (HHMC). Read More

    DYSKERATOSIS CONGENITA IN TWO ETHIOPIAN BROTHERS.
    Ethiop Med J 2015 Oct;53(4):215-21
    Dyskeratosis congenita (DKC) is a rare, progressive bone marrow failure syndrome that is characterized by the triad of reticulated skin pigmentation, nail dystrophy and oral leukoplakia. Current evidence indicates that DKC is a disease of defective telomere maintenance, ribosome deficiency and protein synthesis dysfunction. Mortality is often associated with bone marrow failure (BMF), development of malignancy and other multisystem complications of the disease. Read More

    The shelterin complex and hematopoiesis.
    J Clin Invest 2016 May 2;126(5):1621-9. Epub 2016 May 2.
    Mammalian chromosomes terminate in stretches of repetitive telomeric DNA that act as buffers to avoid loss of essential genetic information during end-replication. A multiprotein complex known as shelterin prevents recognition of telomeric sequences as sites of DNA damage. Telomere erosion contributes to human diseases ranging from BM failure to premature aging syndromes and cancer. Read More

    Bilateral Proliferative Retinopathy Associated With Hoyeraal-Hreidarsson Syndrome, a Severe Form of Dyskeratosis Congenita.
    Ophthalmic Surg Lasers Imaging Retina 2016 Apr;47(4):366-8
    Dyskeratosis congenita (DC) is the prototypical member of a family of diseases caused by defective telomere maintenance. These "telomeropathies" also include Hoyeraal-Hreidarsson syndrome (HH) and Revesz syndrome, which are severe forms of dyskeratosis congenita, as well as a subset of idiopathic pulmonary fibrosis, aplastic anemia, and Coats' plus syndrome. Retinopathy has only rarely been reported in DC and HH, but is universally present in Coats' plus and Revesz syndromes. Read More

    [Clinical and genetic features of dyskeratosis congenital with bone marrow failure in eight patients].
    Zhonghua Xue Ye Xue Za Zhi 2016 Mar;37(3):216-20
    Center of Pediatric Blood Diseases, Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China.
    Objective: To summary clinical and genetic features of childhood dyskeratosis congenital (DC) patients with bone marrow failure.

    Methods: The clinical data of 8 DC patients with bone marrow failure diagnosed between September 2010 and September 2015 were collected. Whole exons with flanking regions of the 16 telomere-related genes, including DKC1, TERC, TERT, NOP10, NHP2, TINF2 and so on, were analyzed by next generation sequence. Read More

    p53 downregulates the Fanconi anaemia DNA repair pathway.
    Nat Commun 2016 Apr 1;7:11091. Epub 2016 Apr 1.
    Genetics of Tumour Suppression, Equipe Labellisée Ligue, Institut Curie, Centre de recherche, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
    Germline mutations affecting telomere maintenance or DNA repair may, respectively, cause dyskeratosis congenita or Fanconi anaemia, two clinically related bone marrow failure syndromes. Mice expressing p53(Δ31), a mutant p53 lacking the C terminus, model dyskeratosis congenita. Accordingly, the increased p53 activity in p53(Δ31/Δ31) fibroblasts correlated with a decreased expression of 4 genes implicated in telomere syndromes. Read More

    Frosted Branch Angiitis in Pediatric Dyskeratosis Congenita: A Case Report.
    Medicine (Baltimore) 2016 Mar;95(12):e3106
    From the Department of Ophthalmology (X-YZ, C-PS); Department of Hematology-Oncology (S-SL); Department of Child Health Care (Z-YZ); Department of Nephrology (J-HM); the Central Lab (WL, XC), The Children's Hospital of Zhejiang University School of Medicine, Hangzhou; and Department of Ophthalmology (JX), the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
    Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome, usually presented with abnormal skin pigmentation, nail dystrophy, and oral leukoplakia. The main cause of mortality in DC is immunodeficiency and vital infection. DC involves multisystem, but retinal involvements are rare. Read More

    A POT1 mutation implicates defective telomere end fill-in and telomere truncations in Coats plus.
    Genes Dev 2016 Apr 24;30(7):812-26. Epub 2016 Mar 24.
    The Rockefeller University, New York, New York 10065, USA;
    Coats plus (CP) can be caused by mutations in the CTC1 component of CST, which promotes polymerase α (polα)/primase-dependent fill-in throughout the genome and at telomeres. The cellular pathology relating to CP has not been established. We identified a homozygous POT1 S322L substitution (POT1(CP)) in two siblings with CP. Read More

    Survival after Hematopoietic Stem Cell Transplant in Patients with Dyskeratosis Congenita: Systematic Review of the Literature.
    Biol Blood Marrow Transplant 2016 Jul 8;22(7):1152-8. Epub 2016 Mar 8.
    Sydney Children's Hospital Network, Sydney, New South Wales, Australia.
    Dyskeratosis congenita (DC) is a multisystem disorder, with a disruption in telomere biology leading to very short telomeres underpinning its pathophysiology. Bone marrow failure is a key feature in DC and is the leading cause of mortality. Hematopoietic stem cell transplantation (HSCT) is the only curative option for bone marrow failure in DC; however, small case reports and series have suggested a poor outcome after HSCT. Read More

    Novel Mutation in the DKC1 Gene: Neonatal Hoyeraal-Hreidarsson Syndrome As a Rare Differential Diagnosis in Pontocerebellar Hypoplasia, Primary Microcephaly, and Progressive Bone Marrow Failure.
    Neuropediatrics 2016 Jun 7;47(3):182-6. Epub 2016 Mar 7.
    Abteilung Neuropädiatrie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße, Dresden, Germany.
    Primary microcephaly and severe developmental delay are complex but unspecific signs pointing to various genetic or acquired diseases. A concomitant finding of hematological failure may lead to the differential diagnosis of rare genetic diseases such as chromosome breakage disorders or diseases associated with telomere dysfunction. X-linked Hoyeraal-Hreidarsson syndrome (HHS) is a rare heterogenic disorder characterized by severe neurological impairment and progressive bone marrow failure. Read More

    Inhibition of telomerase RNA decay rescues telomerase deficiency caused by dyskerin or PARN defects.
    Nat Struct Mol Biol 2016 Apr 7;23(4):286-92. Epub 2016 Mar 7.
    Department of Chemistry &Biochemistry, University of Colorado, Boulder, Colorado, USA.
    Mutations in the human telomerase RNA component (hTR), the telomerase ribonucleoprotein component dyskerin (DKC1) and the poly(A) RNase (PARN) can lead to reduced levels of hTR and to dyskeratosis congenita (DC). However, the enzymes and mechanisms responsible for hTR degradation are unknown. We demonstrate that defects in dyskerin binding lead to hTR degradation by PAPD5-mediated oligoadenylation, which promotes 3'-to-5' degradation by EXOSC10, as well as decapping and 5'-to-3' decay by the cytoplasmic DCP2 and XRN1 enzymes. Read More

    DNA methylation in PRDM8 is indicative for dyskeratosis congenita.
    Oncotarget 2016 Mar;7(10):10765-72
    Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical Faculty, Aachen, Germany.
    Dyskeratosis congenita (DKC) is associated with impaired telomere maintenance and with clinical features of premature aging. In this study, we analysed global DNA methylation (DNAm) profiles of DKC patients. Age-associated DNAm changes were not generally accelerated in DKC, but there were significant differences to DNAm patterns of healthy controls, particularly in CpG sites related to an internal promoter region of PR domain containing 8 (PRDM8). Read More

    Ocular manifestations of genetic skin disorders.
    Clin Dermatol 2016 Mar-Apr;34(2):242-75. Epub 2015 Dec 2.
    The Vision Center, Children's Hospital Los Angeles; Department of Ophthalmology, Keck School of Medicine, University of Southern California, 4650 Sunset Blvd, MS #88, Los Angeles, CA, 90027.
    Genetic skin diseases, or genodermatoses, often have extracutaneous manifestations. Ocular manifestations in particular can have significant clinical implications, like blindness. Other manifestations, such as the corneal opacities that occur in X-linked ichthyosis, are asymptomatic but characteristic of a particular genodermatosis. Read More

    Liver Transplantation After Bone Marrow Transplantation for End Stage Liver Disease with Severe Hepatopulmonary Syndrome in Dyskeratosis Congenita: A Literature First.
    J Clin Exp Hepatol 2015 Dec 12;5(4):344-7. Epub 2015 Nov 12.
    Liver Transplantation & HPB Surgery, Institute of Liver & Biliary Sciences, New Delhi, India.
    Dyskeratosis congenita is a multisystem genetic disorder. Although hepatic involvement is reported in about 7% of patients with dyskeratosis congenita, it is not well characterized and often attributed to hemochromatosis from frequent blood transfusions. A few case reports describe cirrhosis and hepatic cell necrosis in affected individuals in autosomal dominant pedigrees. Read More

    Familial skin cancer syndromes: Increased risk of nonmelanotic skin cancers and extracutaneous tumors.
    J Am Acad Dermatol 2016 Mar;74(3):437-51; quiz 452-4
    Department of Dermatology, Stanford University Medical Center, Stanford, California. Electronic address:
    Nonmelanoma skin cancers (NMSCs) represent the most common malignancies worldwide, with reported incidence rising each year. Both cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), as well as other NMSCs, represent complex diseases with a combination of environmental and genetic risk factors. In general, hereditary cancer syndromes that increase the risk of NMSC fall under several broad categories: those associated with immunodeficiencies, those that affect skin pigmentation, and those that perturb key molecular pathways involved in the pathogenesis of NMSCs. Read More

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