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    1666 results match your criteria Bloom Syndrome Congenital Telangiectatic Erythema

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    Enhancement of BLM-DNA2-Mediated Long-Range DNA End Resection by CtIP.
    Cell Rep 2017 Oct;21(2):324-332
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address:
    DNA double-strand break repair by homologous recombination entails the resection of DNA ends to reveal ssDNA tails, which are used to invade a homologous DNA template. CtIP and its yeast ortholog Sae2 regulate the nuclease activity of MRE11 in the initial stage of resection. Deletion of CtIP in the mouse or SAE2 in yeast engenders a more severe phenotype than MRE11 nuclease inactivation, indicative of a broader role of CtIP/Sae2. Read More

    Successful treatment of community-acquired methicillin-resistant Staphylococcus aureus purulent myopericarditis.
    BMJ Case Rep 2017 Oct 10;2017. Epub 2017 Oct 10.
    Department of Cardiology, Naval Medical Center Portsmouth, Portsmouth, Virginia, USA.
    A previously healthy 48-year-old active duty man, who had been treated for an elbow abscess 3 weeks earlier, presented to an emergency department in Bahrain with tachycardia, pericardial friction rub and jugular venous distention. Cardiac tamponade was confirmed on transthoracic echocardiogram and he was taken for emergent pericardiocentesis. Pericardial fluid cultures grew community-acquired methicillin-resistant Staphylococcus aureus Despite ongoing treatment with intravenous vancomycin, he developed a recurrent fibrinous pericardial effusion and constrictive pericarditis requiring pericardiectomy. Read More

    A New BRCT Binding Mode in TopBP1-BLM Helicase Interaction.
    Structure 2017 Oct 3;25(10):1471-1472. Epub 2017 Oct 3.
    Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA. Electronic address:
    Tandem BRCT domains are phophoprotein binding modules. In this issue of Structure, Sun et al. (2017) show that a single BRCT domain in TopBP1 binds tightly and specifically to phosphorylated Bloom syndrome helicase (BLM). Read More

    Clinical Report: Warsaw Breakage Syndrome with small radii and fibulae.
    Am J Med Genet A 2017 Sep 28. Epub 2017 Sep 28.
    Division of Genetics, Department of Pediatrics, University of California, San Francisco, California.
    We present two new cases of Warsaw Breakage Syndrome (WABS), an autosomal recessive cohesinopathy, in sisters aged 13 and 11 years who both had compound heterozygous mutations in DDX11. After exclusion of Fanconi anemia, Bloom syndrome and Nijmegen breakage syndrome, whole exome sequencing revealed two novel variants-c.1523T>G, predicting (p. Read More

    RecQ helicase BLM regulates prostate cancer cell proliferation and apoptosis.
    Oncol Lett 2017 Oct 2;14(4):4206-4212. Epub 2017 Aug 2.
    Institute of Uro-Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
    Prostate cancer (PCa) is a common malignant tumor and the second leading cause of morbidity and mortality in men worldwide. Considering the prevalence and effects of PCa in males, an understanding of the molecular mechanisms underlying PCa tumorigenesis are essential and may provide novel therapeutic strategies for treating PCa. Bloom syndrome protein (BLM) is a member of the RecQ helicase family. Read More

    Structural Insight into BLM Recognition by TopBP1.
    Structure 2017 Oct 14;25(10):1582-1588.e3. Epub 2017 Sep 14.
    Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada. Electronic address:
    Topoisomerase IIβ binding protein 1 (TopBP1) is a critical protein-protein interaction hub in DNA replication checkpoint control. It was proposed that TopBP1 BRCT5 interacts with Bloom syndrome helicase (BLM) to regulate genome stability through either phospho-Ser304 or phospho-Ser338 of BLM. Here we show that TopBP1 BRCT5 specifically interacts with the BLM region surrounding pSer304, not pSer338. Read More

    BLM and SLX4 play opposing roles in recombination-dependent replication at human telomeres.
    EMBO J 2017 Oct 6;36(19):2907-2919. Epub 2017 Sep 6.
    Telomere Length Regulation Unit, Children's Medical Research Institute, University of Sydney, Westmead, NSW, Australia
    Alternative lengthening of telomeres (ALT) is a telomere lengthening pathway that predominates in aggressive tumors of mesenchymal origin; however, the underlying mechanism of telomere synthesis is not fully understood. Here, we show that the BLM-TOP3A-RMI (BTR) dissolvase complex is required for ALT-mediated telomere synthesis. We propose that recombination intermediates formed during strand invasion are processed by the BTR complex, initiating rapid and extensive POLD3-dependent telomere synthesis followed by dissolution, with no overall exchange of telomeric DNA. Read More

    A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial.
    Hum Reprod 2017 Sep;32(9):1915-1924
    Department of Investigative Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.
    Study Question: Can increasing the duration of LH-exposure with a second dose of kisspeptin-54 improve oocyte maturation in women at high risk of ovarian hyperstimulation syndrome (OHSS)?

    Summary Answer: A second dose of kisspeptin-54 at 10 h following the first improves oocyte yield in women at high risk of OHSS.

    What Is Known Already: Kisspeptin acts at the hypothalamus to stimulate the release of an endogenous pool of GnRH from the hypothalamus. We have previously reported that a single dose of kisspeptin-54 results in an LH-surge of ~12-14 h duration, which safely triggers oocyte maturation in women at high risk of OHSS. Read More

    Recurrent glomerular disease after kidney transplantation.
    Curr Opin Nephrol Hypertens 2017 Nov;26(6):501-508
    aDepartment of Medicine, Division of Nephrology, University of Washington, Washington bDepartment of Medicine, Renal Division, University of Pennsylvania cDepartment of Medicine, Penn Transplant Institute, Pennsylvania, USA.
    Purpose Of Review: With improving short-term kidney transplant outcomes, recurrent glomerular disease is being increasingly recognized as an important cause of chronic allograft failure. Further understanding of the risks and pathogenesis of recurrent glomerular disease enable informed transplant decisions, along with the development of preventive and treatment strategies.

    Recent Findings: Multiple observational studies have highlighted differences in rates and outcomes for various recurrent glomerular diseases, although these rates have not markedly improved over the last decade. Read More

    Bloom syndrome helicase in meiosis: Pro-crossover functions of an anti-crossover protein.
    Bioessays 2017 Sep 9;39(9). Epub 2017 Aug 9.
    Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
    The functions of the Bloom syndrome helicase (BLM) and its orthologs are well characterized in mitotic DNA damage repair, but their roles within the context of meiotic recombination are less clear. In meiotic recombination, multiple repair pathways are used to repair meiotic DSBs, and current studies suggest that BLM may regulate the use of these pathways. Based on literature from Saccharomyces cerevisiae, Arabidopsis thaliana, Mus musculus, Drosophila melanogaster, and Caenorhabditis elegans, we present a unified model for a critical meiotic role of BLM and its orthologs. Read More

    DNA2-An Important Player in DNA Damage Response or Just Another DNA Maintenance Protein?
    Int J Mol Sci 2017 Jul 18;18(7). Epub 2017 Jul 18.
    Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland.
    The human DNA2 (DNA replication helicase/nuclease 2) protein is expressed in both the nucleus and mitochondria, where it displays ATPase-dependent nuclease and helicase activities. DNA2 plays an important role in the removing of long flaps in DNA replication and long-patch base excision repair (LP-BER), interacting with the replication protein A (RPA) and the flap endonuclease 1 (FEN1). DNA2 can promote the restart of arrested replication fork along with Werner syndrome ATP-dependent helicase (WRN) and Bloom syndrome protein (BLM). Read More

    A Recessive Genetic Screen for Components of the RNA Interference Pathway Performed in Mouse Embryonic Stem Cells.
    Methods Mol Biol 2017 ;1622:111-129
    Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Hogan 2-100, 2205 Tech Drive, Evanston, IL, 60208, USA.
    Several key components of the RNA interference (RNAi) pathway were identified in genetic screens performed in non-mammalian model organisms. To identify components of the mammalian RNAi pathway, we developed a recessive genetic screen in mouse embryonic stem (ES) cells. Recessive genetic screens are feasible in ES cells that are Bloom-syndrome protein deficient (Blm-deficient). Read More

    Site-Specific Self-Catalyzed DNA Depurination: A Biological Mechanism That Leads to Mutations and Creates Sequence Diversity.
    Annu Rev Biochem 2017 Jun;86:461-484
    Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544; email: ,
    Self-catalyzed DNA depurination is a sequence-specific physiological mechanism mediated by spontaneous extrusion of a stem-loop catalytic intermediate. Hydrolysis of the 5'G residue of the 5'GA/TGG loop and of the first 5'A residue of the 5'GAGA loop, together with particular first stem base pairs, specifies their hydrolysis without involving protein, cofactor, or cation. As such, this mechanism is the only known DNA catalytic activity exploited by nature. Read More

    Cancer predisposition syndromes associated with myeloid malignancy.
    Semin Hematol 2017 Apr 7;54(2):115-122. Epub 2017 Apr 7.
    Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN. Electronic address:
    The majority of myeloid malignancies are caused by sporadic somatic events rather than cancer predisposition. Nonetheless, the identification of hereditary cancer predisposition syndromes is critical when caring for patients with myeloid malignancies since detection may direct decisions related to cancer treatment and surveillance. A positive genetic test result also has important implications for other family members who can use this information to undergo their own testing to determine their cancer risk. Read More

    First Two Cases of Bloom Syndrome in Russia: Lack of Skin Manifestations in a BLM c.1642C>T (p.Q548X) Homozygote as a Likely Cause of Underdiagnosis.
    Mol Syndromol 2017 Mar 17;8(2):103-106. Epub 2017 Jan 17.
    St. Petersburg State Pediatric Medical University, Kazan, Russia.
    Bloom syndrome (BS) is an exceptionally rare hereditary disease. Typical manifestations of BS usually include growth deficiency, a characteristic facial appearance, skin hypersensitivity to ultraviolet irradiation, and a strong predisposition to early-onset cancers. We have previously described a recurrent BLM c. Read More

    Recommendations for Childhood Cancer Screening and Surveillance in DNA Repair Disorders.
    Clin Cancer Res 2017 Jun;23(11):e23-e31
    National Cancer Institute, Rockville, Maryland.
    DNA repair syndromes are heterogeneous disorders caused by pathogenic variants in genes encoding proteins key in DNA replication and/or the cellular response to DNA damage. The majority of these syndromes are inherited in an autosomal-recessive manner, but autosomal-dominant and X-linked recessive disorders also exist. The clinical features of patients with DNA repair syndromes are highly varied and dependent on the underlying genetic cause. Read More

    Role for RIF1-interacting partner DDX1 in BLM recruitment to DNA double-strand breaks.
    DNA Repair (Amst) 2017 Jul 13;55:47-63. Epub 2017 May 13.
    Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton Alberta T6G 1Z2, Canada. Electronic address:
    Human Rap1-interacting factor 1 (RIF1) is an important player in the repair of DNA double strand breaks (DSBs). RIF1 acts downstream of 53BP1, with well-documented roles in class switch recombination in B-cells and inhibition of end resection initiation in BRCA1-defective cells. Here, we report that DEAD Box 1 (DDX1), a RNA helicase also implicated in DSB repair, interacts with RIF1, with co-localization of DDX1 and RIF1 observed throughout interphase. Read More

    Targeted Next Generation Sequencing Approach in Patients Referred for Silver-Russell Syndrome Testing Increases the Mutation Detection Rate and Provides Decisive Information for Clinical Management.
    J Pediatr 2017 Aug 19;187:206-212.e1. Epub 2017 May 19.
    Institute of Human Genetics, University Hospital, Technical University Aachen (Rheinisch-Westfälische Technische Hochschule), Aachen, Germany. Electronic address:
    Objective: To investigate the contribution of differential diagnoses to the mutation spectrum of patients referred for Silver-Russell syndrome (SRS) testing.

    Study Design: Forty-seven patients referred for molecular testing for SRS were examined after exclusion of one of the SRS-associated alterations. After clinical classification, a targeted next generation sequencing approach comprising 25 genes associated with other diagnoses or postulated as SRS candidate genes was performed. Read More

    Cytidine deaminase deficiency impairs sister chromatid disjunction by decreasing PARP-1 activity.
    Cell Cycle 2017 Jun 2;16(11):1128-1135. Epub 2017 May 2.
    a Institut Curie, PSL Research University, UMR 3348, Unité Stress Génotoxiques et Cancer, Centre de Recherche , Orsay , France.
    Bloom Syndrome (BS) is a rare genetic disease characterized by high levels of chromosomal instability and an increase in cancer risk. Cytidine deaminase (CDA) expression is downregulated in BS cells, leading to an excess of cellular dC and dCTP that reduces basal PARP-1 activity, compromising optimal Chk1 activation and reducing the efficiency of downstream checkpoints. This process leads to the accumulation of unreplicated DNA during mitosis and, ultimately, ultrafine anaphase bridge (UFB) formation. Read More

    The absence of crossovers on chromosome 4 in Drosophila melanogaster: Imperfection or interesting exception?
    Fly (Austin) 2017 Apr 20:1-7. Epub 2017 Apr 20.
    a Curriculum in Genetics and Molecular Biology , University of North Carolina , Chapel Hill , North Carolina , USA.
    Drosophila melanogaster chromosome 4 is an anomaly because of its small size, chromatin structure, and most notably its lack of crossing over during meiosis. Earlier ideas about the absence of crossovers on 4 hypothesize that these unique characteristics function to prevent crossovers. Here, we explore hypotheses about the absence of crossovers on 4, how these have been addressed, and new insights into the mechanism behind this suppression. Read More

    [Hereditary bone tumors].
    Pathologe 2017 May;38(3):179-185
    Institut für Pathologie, Knochentumor-Referenzzentrum, Universitätsspital Basel, Schönbeinstrasse 40, 4031, Basel, Schweiz.
    Hereditary bone tumors are rare and result from mutations affecting cell cycle regulation (e.g. retinoblastoma syndrome/RB1 and Li-Fraumeni syndrome/TP53, Gardner syndrome/APC), energy metabolism (enchondromatosis/IDH1/2), complex signaling cascades (multiple hereditary exostoses/EXT1/2) and DNA integrity (Rothmund-Thomson/RECQL4, Werner/WRN and Bloom syndromes/BLM). Read More

    Purification and enzymatic characterization of Gallus gallus BLM helicase.
    J Biochem 2017 Sep;162(3):183-191
    College of Life Sciences, Northwest A&F University, Yangling, Shaanxi 712100, China.
    Mutations in human BLM helicase give rise to the autosomal recessive Bloom syndrome, which shows high predisposition to types of malignant tumours. Though lots of biochemical and structural investigations have shed lights on the helicase core, structural investigations of the whole BLM protein are still limited due to its low stability and production. Here by comparing with the expression systems and functions of other BLM homologues, we developed the heterologous high-level expression and high-yield purification systems for Gallus gallus BLM (gBLM) in Escherichia coli. Read More

    A prosurvival DNA damage-induced cytoplasmic interferon response is mediated by end resection factors and is limited by Trex1.
    Genes Dev 2017 Feb 9;31(4):353-369. Epub 2017 Mar 9.
    Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom.
    Radiotherapy and chemotherapy are effective treatment methods for many types of cancer, but resistance is common. Recent findings indicate that antiviral type I interferon (IFN) signaling is induced by these treatments. However, the underlying mechanisms still need to be elucidated. Read More

    Bloom's Syndrome: Clinical Spectrum, Molecular Pathogenesis, and Cancer Predisposition.
    Mol Syndromol 2017 Jan 5;8(1):4-23. Epub 2016 Nov 5.
    Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, Tucson, Ariz., USA.
    Bloom's syndrome is an autosomal recessive disorder characterized by prenatal and postnatal growth deficiency, photosensitive skin changes, immune deficiency, insulin resistance, and a greatly increased risk of early onset of cancer and for the development of multiple cancers. Loss-of-function mutations of BLM, which codes for a RecQ helicase, cause Bloom's syndrome. The absence of a functional BLM protein causes chromosome instability, excessive homologous recombination, and a greatly increased number of sister chromatid exchanges that are pathognomonic of the syndrome. Read More

    A helical bundle in the N-terminal domain of the BLM helicase mediates dimer and potentially hexamer formation.
    J Biol Chem 2017 Apr 22;292(14):5909-5920. Epub 2017 Feb 22.
    From the College of Life Sciences, Northwest A&F University, Yangling, Shaanxi 712100, China,
    Helicases play a critical role in processes such as replication or recombination by unwinding double-stranded DNA; mutations of these genes can therefore have devastating biological consequences. In humans, mutations in genes of three members of the RecQ family helicases (blm, wrn, and recq4) give rise to three strikingly distinctive clinical phenotypes: Bloom syndrome, Werner syndrome, and Rothmund-Thomson syndrome, respectively. However, the molecular basis for these varying phenotypic outcomes is unclear, in part because a full mechanistic description of helicase activity is lacking. Read More

    Identifying the incidence of rash, Stevens-Johnson syndrome and toxic epidermal necrolysis in patients taking lamotrigine: a systematic review of 122 randomized controlled trials.
    An Bras Dermatol 2017 Jan-Feb;92(1):139-141
    University of California Irvine, Department of Dermatology - Irvine, California.
    Lamotrigine is an antiepileptic drug used for the treatment of epilepsy, bipolar disorder and numerous off-label uses. The development of rash significantly affects its use. The most concerning of these adverse reactions is Stevens-Johnson syndrome/toxic epidermal necrolysis. Read More

    Prognostic Accuracy of Sepsis-3 Criteria for In-Hospital Mortality Among Patients With Suspected Infection Presenting to the Emergency Department.
    JAMA 2017 01;317(3):301-308
    Emergency Department, Hôpital Ambroise-Paré, Boulogne, France, and Paris Diderot University, INSERM UMRS 1144, Paris, France.
    Importance: An international task force recently redefined the concept of sepsis. This task force recommended the use of the quick Sequential Organ Failure Assessment (qSOFA) score instead of systemic inflammatory response syndrome (SIRS) criteria to identify patients at high risk of mortality. However, these new criteria have not been prospectively validated in some settings, and their added value in the emergency department remains unknown. Read More

    Oxidative stress, mitochondrial abnormalities and antioxidant defense in Ataxia-telangiectasia, Bloom syndrome and Nijmegen breakage syndrome.
    Redox Biol 2017 Apr 28;11:375-383. Epub 2016 Dec 28.
    Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna 37 Str., 15-295 Bialystok, Poland. Electronic address:
    Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are characterised by immunodeficiency, extreme radiosensitivity, higher cancer susceptibility, premature aging, neurodegeneration and insulin resistance. Some of these functional abnormalities can be explained by aberrant DNA damage response and chromosomal instability. It has been suggested that one possible common denominator of these conditions could be chronic oxidative stress caused by endogenous ROS overproduction and impairment of mitochondrial homeostasis. Read More

    Bloom syndrome complex promotes FANCM recruitment to stalled replication forks and facilitates both repair and traverse of DNA interstrand crosslinks.
    Cell Discov 2016 20;2:16047. Epub 2016 Dec 20.
    Lab of Genetics, National Institute on Aging, National Institute of Health , Baltimore, MD, USA.
    The recruitment of FANCM, a conserved DNA translocase and key component of several DNA repair protein complexes, to replication forks stalled by DNA interstrand crosslinks (ICLs) is a step upstream of the Fanconi anemia (FA) repair and replication traverse pathways of ICLs. However, detection of the FANCM recruitment has been technically challenging so that its mechanism remains exclusive. Here, we successfully observed recruitment of FANCM at stalled forks using a newly developed protocol. Read More

    Bloom Syndrome Helicase Promotes Meiotic Crossover Patterning and Homolog Disjunction.
    Curr Biol 2017 Jan 15;27(1):96-102. Epub 2016 Dec 15.
    Curriculum in Genetics and Molecular Biology, 120 Mason Farm Road, University of North Carolina, Chapel Hill, NC 27599-7264, USA; Department of Biology, University of North Carolina, 120 South Road, Chapel Hill, NC 27599-3280, USA; Integrative Program in Biological and Genome Sciences, 250 Bell Tower Drive, University of North Carolina, Chapel Hill, NC 27599-7100, USA. Electronic address:
    In most sexually reproducing organisms, crossover formation between homologous chromosomes is necessary for proper chromosome disjunction during meiosis I. During meiotic recombination, a subset of programmed DNA double-strand breaks (DSBs) are repaired as crossovers, with the remainder becoming noncrossovers [1]. Whether a repair intermediate is designated to become a crossover is a highly regulated decision that integrates several crossover patterning processes, both along chromosome arms (interference and the centromere effect) and between chromosomes (crossover assurance) [2]. Read More

    Loss of RMI2 Increases Genome Instability and Causes a Bloom-Like Syndrome.
    PLoS Genet 2016 Dec 15;12(12):e1006483. Epub 2016 Dec 15.
    Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Parkville, Victoria, Australia.
    Bloom syndrome is a recessive human genetic disorder with features of genome instability, growth deficiency and predisposition to cancer. The only known causative gene is the BLM helicase that is a member of a protein complex along with topoisomerase III alpha, RMI1 and 2, which maintains replication fork stability and dissolves double Holliday junctions to prevent genome instability. Here we report the identification of a second gene, RMI2, that is deleted in affected siblings with Bloom-like features. Read More

    Successful treatment of mature B-cell lymphoma with rituximab-based chemotherapy in a patient with Bloom syndrome.
    Pediatr Blood Cancer 2017 Jul 14;64(7). Epub 2016 Dec 14.
    College of Medicine, Department of Pediatrics, Umm AlQura University, Makkah, Saudi Arabia.
    This report presents a case of Bloom syndrome (BS) in a consanguineous Saudi family. The patient, an 11-year-old male with mature B-cell lymphoma, had minimal therapeutic response and significant dose-limiting toxicity with standard chemotherapy treatment. He later responded successfully to a rituximab-based chemotherapy protocol. Read More

    BLM germline and somatic PKMYT1 and AHCY mutations: Genetic variations beyond MYCN and prognosis in neuroblastoma.
    Med Hypotheses 2016 Dec 20;97:22-25. Epub 2016 Oct 20.
    Instituto de Tratamento de Câncer Infantil (ITACI), Pediatric Department at São Paulo University Medical School, Hematology-Oncology Division, São Paulo, SP, Brazil; Hospital Israelita Albert Einstein (HIAE), Hematology Oncology Division, São Paulo, SP, Brazil.
    Neuroblastoma (NB) is the most common extra cranial solid tumor of childhood and often lethal in childhood. Clinical and biologic characteristics that are independently prognostic of outcome in NB are currently used for risk stratification to optimally the therapy. It includes age at diagnosis, International Neuroblastoma Staging System tumor histopathology and MYCN amplification. Read More

    [Bloom syndrome. Clinical manifestations and cromosomal study in a Mexican child].
    Gac Med Mex 2016 Nov - Dec;152(6):836-837
    Departamento de Dermatología, Hospital Universitario Dr. José Eleuterio González, Universidad Autónoma de Nuevo León, Monterrey, N.L., México.
    Bloom syndrome is an extremely rare inherited disorder. We present a case of Bloom syndrome with a chromosomal study in a Mexican five-year-old patient who presented growth retardation, narrow facies with poikiloderma, café-au-lait, macules and photosensitivity. Read More

    Human RECQ Helicase Pathogenic Variants, Population Variation and "Missing" Diseases.
    Hum Mutat 2017 Feb 9;38(2):193-203. Epub 2016 Dec 9.
    Department of Genome Sciences, University of Washington, Seattle, Washington.
    Heritable loss of function mutations in the human RECQ helicase genes BLM, WRN, and RECQL4 cause Bloom, Werner, and Rothmund-Thomson syndromes, cancer predispositions with additional developmental or progeroid features. In order to better understand RECQ pathogenic and population variation, we systematically analyzed genetic variation in all five human RECQ helicase genes. A total of 3,741 unique base pair-level variants were identified, across 17,605 potential mutation sites. Read More

    The Werner Syndrome Helicase Coordinates Sequential Strand Displacement and FEN1-Mediated Flap Cleavage during Polymerase δ Elongation.
    Mol Cell Biol 2017 Feb 19;37(3). Epub 2017 Jan 19.
    Department of Molecular Microbiology and Immunology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
    The Werner syndrome protein (WRN) suppresses the loss of telomeres replicated by lagging-strand synthesis by a yet to be defined mechanism. Here, we show that whereas either WRN or the Bloom syndrome helicase (BLM) stimulates DNA polymerase δ progression across telomeric G-rich repeats, only WRN promotes sequential strand displacement synthesis and FEN1 cleavage, a critical step in Okazaki fragment maturation, at these sequences. Helicase activity, as well as the conserved winged-helix (WH) motif and the helicase and RNase D C-terminal (HRDC) domain play important but distinct roles in this process. Read More

    RMND1-Related Leukoencephalopathy With Temporal Lobe Cysts and Hearing Loss-Another Mendelian Mimicker of Congenital Cytomegalovirus Infection.
    Pediatr Neurol 2017 Jan 13;66:59-62. Epub 2016 Sep 13.
    Department of Neurology, Children's National Medical Center, Washington, DC; Department of Integrated Systems Biology, George Washington University, Washington, DC; Department of Pediatrics, George Washington University, Washington, DC. Electronic address:
    Background: Leukoencephalopathy with temporal lobe cysts may be associated with monogenetic conditions such as Aicardi-Goutières syndrome or RNASET2 mutations and with congenital infections such as cytomegalovirus. In view of the fact that congenital cytomegalovirus is difficult to confirm outside the neonatal period, excluding a Mendelian disorder is extremely relevant, changing family planning and medical management in affected families. We performed diagnostic testing in individuals with leukoencephalopathy with temporal lobe cysts without a definitive diagnosis of congenital cytomegalovirus infection. Read More

    Neurodegeneration in accelerated aging.
    Dan Med J 2016 Nov;63(11)
    The growing proportion of elderly people represents an increasing economic burden, not least because of age-associated diseases that pose a significant cost to the health service. Finding possible interventions to age-associated disorders therefore have wide ranging implications. A number of genetically defined accelerated aging diseases have been characterized that can aid in our understanding of aging. Read More

    Congenital and perinatal complications of chikungunya fever: a Latin American experience.
    Int J Infect Dis 2016 Oct 13;51:85-88. Epub 2016 Sep 13.
    Centro Médico UCE, Santo Domingo, Dominican Republic.
    Background: During the years 2014 and 2015, the Region of the Americas underwent a devastating epidemic of chikungunya virus (CHIKV) of the Asian genotype, resulting in millions of affected individuals. However, epidemiological and clinical information on this experience is scarce. Prior knowledge of congenital and neonatal illness caused by CHIKV is limited and almost exclusively based on data obtained from a single outbreak of the East/Central/South African (ECSA) genotype. Read More

    Understanding photodermatoses associated with defective DNA repair: Syndromes with cancer predisposition.
    J Am Acad Dermatol 2016 Nov;75(5):855-870
    Department of Dermatology, Henry Ford Hospital, Detroit, Michigan. Electronic address:
    Hereditary photodermatoses are a spectrum of rare photosensitive disorders that are often caused by genetic deficiency or malfunction of various components of the DNA repair pathway. This results clinically in extreme photosensitivity, with many syndromes exhibiting an increased risk of cutaneous malignancies. This review will focus specifically on the syndromes with malignant potential, including xeroderma pigmentosum, Bloom syndrome, and Rothmund-Thomson syndrome. Read More

    Human Resources for Treating HIV/AIDS: Are the Preventive Effects of Antiretroviral Treatment a Game Changer?
    PLoS One 2016 7;11(10):e0163960. Epub 2016 Oct 7.
    Amazon.com, Inc., Seattle, Washington, United States of America.
    Shortages of human resources for treating HIV/AIDS (HRHA) are a fundamental barrier to reaching universal antiretroviral treatment (ART) coverage in developing countries. Previous studies suggest that recruiting HRHA to attain universal ART coverage poses an insurmountable challenge as ART significantly increases survival among HIV-infected individuals. While new evidence about ART's prevention benefits suggests fewer infections may mitigate the challenge, new policies such as treatment-as-prevention (TasP) will exacerbate it. Read More

    Clinically significant cardiopulmonary events and the effect of definition standardization on apnea of prematurity management.
    J Perinatol 2017 Jan 29;37(1):88-90. Epub 2016 Sep 29.
    Department of Neonatology, Wichita Medical Research and Education Foundation, Wichita, KS, USA.
    Objective: To define the impact of care standardization on caffeine and cardiorespiratory monitoring at neonatal intensive care unit (NICU) discharge.

    Study Design: Electronic records were abstracted for infants aged 24-36 weeks gestation with birth weights appropriate for gestational age. Infants who died, transferred prior to discharge, had major pulmonary anomalies, required a home monitor for mechanical ventilation or had a family history of sudden infant death syndrome were excluded. Read More

    Extensive nuclear sphere generation in the human Alzheimer's brain.
    Neurobiol Aging 2016 Dec 26;48:103-113. Epub 2016 Aug 26.
    Cell Signaling in Neurodegeneration (CSIN), Medical Proteome-Center, Ruhr-University Bochum, Universitätsstr. 150, Bochum, Germany. Electronic address:
    Nuclear spheres are protein aggregates consisting of FE65, TIP60, BLM, and other yet unknown proteins. Generation of these structures in the cellular nucleus is putatively modulated by the amyloid precursor protein (APP), either by its cleavage or its phosphorylation. Nuclear spheres were preferentially studied in cell culture models and their existence in the human brain had not been known. Read More


    Joint SOGC-CCMG Opinion for Reproductive Genetic Carrier Screening: An Update for All Canadian Providers of Maternity and Reproductive Healthcare in the Era of Direct-to-Consumer Testing.
    J Obstet Gynaecol Can 2016 Aug;38(8):742-762.e3
    Vancouver BC.
    Objective: This guideline was written to update Canadian maternity care and reproductive healthcare providers on pre- and postconceptional reproductive carrier screening for women or couples who may be at risk of being carriers for autosomal recessive (AR), autosomal dominant (AD), or X-linked (XL) conditions, with risk of transmission to the fetus. Four previous SOGC- Canadian College of Medical Geneticists (CCMG) guidelines are updated and merged into the current document.

    Intended Users: All maternity care (most responsible health provider [MRHP]) and paediatric providers; maternity nursing; nurse practitioner; provincial maternity care administrator; medical student; and postgraduate resident year 1-7. Read More

    Cytidine Deaminase Deficiency Reveals New Therapeutic Opportunities against Cancer.
    Clin Cancer Res 2017 Apr 6;23(8):2116-2126. Epub 2016 Sep 6.
    Institut Curie, PSL Research University, UMR 3348, 91405 Orsay, France.
    Purpose: One of the main challenges in cancer therapy is the identification of molecular mechanisms mediating resistance or sensitivity to treatment. Cytidine deaminase (CDA) was reported to be downregulated in cells derived from patients with Bloom syndrome, a genetic disease associated with a strong predisposition to a wide range of cancers. The purpose of this study was to determine whether CDA deficiency could be associated with tumors from the general population and could constitute a predictive marker of susceptibility to antitumor drugs. Read More

    Mutator Phenotype and DNA Double-Strand Break Repair in BLM Helicase-Deficient Human Cells.
    Mol Cell Biol 2016 Dec 14;36(23):2877-2889. Epub 2016 Nov 14.
    Division of Genetics and Mutagenesis, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan
    Bloom syndrome (BS), an autosomal recessive disorder of the BLM gene, predisposes sufferers to various cancers. To investigate the mutator phenotype and genetic consequences of DNA double-strand breaks (DSBs) in BS cells, we developed BLM helicase-deficient human cells by disrupting the BLM gene. Cells with a loss of heterozygosity (LOH) due to homologous recombination (HR) or nonhomologous end joining (NHEJ) can be restored with or without site-directed DSB induction. Read More

    Adenocarcinoma of the Right Colon in a Patient with Bloom Syndrome.
    Case Rep Surg 2016 15;2016:3176842. Epub 2016 Aug 15.
    Division of Colorectal Surgery, University of Campinas, Campinas, SP, Brazil.
    Introduction. Bloom syndrome (BS) is an inherited disorder due to mutation in BLM gene. The diagnosis of BS should be considered in patients with growth retardation of prenatal onset, a photosensitive rash in a butterfly distribution over the cheeks, and an increased risk of cancer at an early age. Read More

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