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Comprehensive Platelet Disorder Panel

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References Mumford AD, Nisar S et al. 2013. Platelet dysfunction associated with the novel Trp29Cys thromboxane A₂ receptor variant. J Thromb Haemost. Mar;11(3):547-54. Albers CA, Paul DS et al. 2012. Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A Noris P, Biino G et al. 2014. Platelet diameters in inherited thrombocytopenias: causes TAR syndrome. Nat Genet. 2012 Feb 26; 44(4):435-9. analysis of 376 patients with all known disorders. Blood. Aug 7; 124(6):e4-e10. Comprehensive Ali S, Ghosh K et al. 2016. Congenital macrothrombocytopenia is a heterogeneous Noris P, Favier R et al. 2013. ANKRD26-related thrombocytopenia and myeloid disorder in India. Haemophilia. Jul; 22(4):570-82. malignancies. Blood .122:1987-1989. Balduini CL, Pecci A, Savoia A. 2011. Recent advances in the understanding and Nurden AT, Nurden P. 2011. Advances in our understanding of the molecular basis management of MYH9-related inherited thrombocytopenias. Br J Haematol. of disorders of platelet function. J Thromb Haemost. 9 Suppl 1:76-91. Jul;154(2):161-174. Nurden AT, Nurden P. 2015. Inherited disorders of platelet function: selected Platelet Disorder Balduini CL, Melazzini F, Pecci A. 2017. Inherited thrombocytopenias-recent updates. J Thromb Haemost. Volume 13(Suppl1): S2- S9. advances in clinical and molecular aspects. Platelets. Jan;28(1):3-13. Ok Bozkaya I, Yarali N et al. Severe Clinical Course in a Patient with Congenital Bastida JM, Del Rey M et al. 2016. Wiskott-Aldrich syndrome in a child presenting Amegakaryocytic Thrombocytopenia Due to a Missense Mutation of the c-MPL with macrothrombocytopenia. Platelets.Nov 25:1-4. Gene. Turk J Haematol.Jun; 32(2): 172-4. Panel Bottega R, Marconi C et al. 2015. ACTN1-related thrombocytopenia: identification Pagel J, Beutel K et al. 2012. Distinct mutations in STXBP2 are associated of novel families for phenotypic characterization. Blood. Jan 29;125(5):748-50. with variable clinical presentations in patients with familial hemophagocytic lymphohistiocytosis type 5 (FHL5). Blood. 119:6016-6024. Cox K, Price V, Kahr WHA. 2011. Inherited platelet disorders: a clinical approach to diagnosis and management. Expert Rev Hematol. Aug;4(4):455-72. Paterson AD, Rommens JM, et al. 2010. Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene. difficult to interpret, and typically require immediate testing on Faioni EM, Razzari C et al. 2014. Bleeding diathesis and gastro-duodenal ulcers Blood.115:1264-6. BloodCenter of Wisconsin offers a specifically in inherited cytosolic phospholipase-A2 alpha deficiency. Thromb Haemost. fresh patient platelets due to limited sample stability. Advances in Dec;112(6):1182-9. Rao AK. 2013. Inherited platelet function disorders: overview and disorders of designed Comprehensive Platelet Disorder granules, secretion, and signal transduction. Hematol Oncol Clin North Am. Jun; genetic testing through next-generation sequencing allows for Favier R, Raslova H. 2015. Progress in understanding the diagnosis and molecular 27(3):585-611. Panel (test code 4830) optimized for detection identification of underlying genetic defects and for distinguishing genetics of macrothrombocytopenias. Br J Haematol. Sep;170 (5):626-39. Rehm HL, Bale SJ et al. 2013. Working Group of the American College of Medical of germline variants in 43 genes known to inherited platelet disorder cases from immune thrombocytopenia. Freson K, Wijgaerts A, Van Geet C. 2014. Update on the causes of platelet disorders Genetics and Genomics Laboratory Quality Assurance Committee. ACMG clinical cause platelet function disorders and/or Accurate diagnosis provides information about the phenotype and functional consequences. John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 36, laboratory standards for next-generation sequencing. Genet Med.15:733-747. and prognosis, guides medical management decisions, assists 313–325. Richards S, Aziz N A et al.2015. Standards and guidelines for the interpretation of inherited thrombocytopenia. with the identification of affected family members, and allows for Gresele P. 2014. Diagnosis of inherited platelet function disorders: guidance for the sequence variants: a joint consensus recommendation of the American College accurate genetic recurrence risk assessment. SSC of the ISTH. J Thromb and Haemost. 13:314-322. of Medical Genetics and Genomics and the Association for Molecular Pathology. Gunay-Aygun M, Falik-Zaccai TC et al. 2011. NBEAL2 is mutated in Gray platelet Genet Med.17:405-424. Platelet function disorders and inherited thrombocytopenia are a Variants in several genes known to cause syndromic or non- Syndrome and is required for biogenesis of platelet alpha-granules. Nat Genet. Savoia A. 2016. Molecular basis of Inherited thrombocytopenias. Clin Genet heterogeneous group of disorders which may have overlapping syndromic platelet disorders may be inherited in an autosomal Aug; 43(8): 732–734. Feb;89(2):154-62. clinical phenotypes, generally differentiated by platelet counts. recessive, autosomal dominant or X-linked recessive manner. More Hinckley J, Di Paola J. 2014. Genetic basis of congenital platelet disorders. Savoia A. 2016. Molecular basis of Inherited thrombocytopenias: an update. Inherited thrombocytopenia disorders are typically characterized common and rare types of syndromic or non-syndromic platelet Hematology Am Soc Hematol Educ Program. Dec5;(1): 3337-42. Current Opinion in Hematology. Sep;23(5):486-492. by platelet counts less than 150,000/uL, but often can vary with disorders will be identified with this panel, including MYH9-related Israels SJ, El-Ekiaby M, Quiroga T, Mezzano D. 2010. Inherited disorders of platelet Kunishima Shinji S, Kobayashi R et al. 2009. Mutation of the β1-tubulin gene age, gender and ethnic background, while platelet function disorders, Glanzmann thrombasthenia, Bernard-Soulier syndrome, function and challenges to diagnosis of mucocutaneous bleeding. Haemophilia. associated with congenital macrothrombocytopenia affecting microtubule disorders are usually, but not always, associated with normal congenital amegakaryocytic thrombocytopenia, familial 16 (Suppl 5):152-9. assembly. Blood. 113:458-461. platelet counts and are caused by defects in platelet adhesion, platelet disorder with predisposition for acute myelogenous Johnson B, Lowe GC et al. 2016. Whole exome sequencing identifies genetic Songdej N, Rao AK. 2017. Inherited platelet dysfunction and hematopoietic glycoprotein expression, receptor function, signaling pathways, leukemia, ANKRD26-related thrombocytopenia, WAS-related variants in inherited thrombocytopenia with secondary qualitative function transcription factor mutations. Platelets Jan; 28(1):20-26. aggregation, cytoskeleton proteins, secretion, granular contents thrombocytopenia, Scott syndrome, gray platelet syndrome defects. Haematologica. 101(10):1170-1179. Stevenson WS, Rabbolini DJ et al. 2015. Paris-Trousseau thrombocytopenia is and abnormalities in procoagulant activity. Symptoms of platelet and others. Additional genes on this panel are associated with Kumar R, Kahr WHA. 2013. Congenital Thrombocytopenia: Clinical Manifestations, phenocopied by the autosomal recessive inheritance of a DNA-binding domain disorders may include purpura, petechiae, prolonged bleeding syndromes that have platelet disorders as a common finding Laboratory Abnormalities, and Molecular Defects of a Heterogeneous Group of mutation in FLI1. Blood. Oct 22;126(17); 2027-30. Conditions. Hematol Oncol Clin North Am. June; 27(3):465-94. from cuts, epistaxis, gum bleeding, excessive bleeding after among other non-hematologic features. Watson SP, Lowe M et al. 2013. Genotyping and phenotyping of platelet function surgery, hemoptysis, hematuria and menorrhagia in women. Kunicki TJ, Williams SA, Nugent DJ. 2012. Genetic variants that affect platelet disorders. J Thromb Haemost. 11(suppl.1):351-363. This panel evaluates for single nucleotide variants and small function. Current Opin Hematol.19:371-9. Severe platelet disorders can present in the newborn period, deletions and duplications, which are most commonly responsible Westbury SK, Mumford AD. 2016. Genomics of platelet disorders. Hemophilia. while mild thrombocytopenia may remain undiagnosed until Lentaigne C, Freson K et al. 2016. Inherited platelet disorders: toward DNA-based 22(Suppl.5): 20-24. for genetic disease. However, large deletions and duplications, diagnosis. Blood. 127(23):2814-2823. incidental detection of thrombocytopenia on routine blood also referred to as copy number variants (CNV), are a known cause Zhang My, Churpek JE et al. 2015. Germline ETV6 mutations in familial testing in adulthood. Some inherited platelet disorders have Manchev VT, Hilpert M et al. 2014. A new form of macrothrombocytopenia thrombocytopenia and hematologic malignancy. Nat Genet. Feb; 47(2):180-185. of genetic disorders, but can escape detection by next-generation induced by a germ-line mutation in the PRKACG gene. Blood. Oct 16; only hematologic manifestations, such as differences in platelet sequence analysis. Further testing with BloodCenter of Wisconsin 124(16):2554-63. Zhou Y, Zhang J. 2014. Arthrogryposis–renal dysfunction–cholestasis (ARC) size or distinctive granulocyte inclusions, while other syndromic syndrome: from molecular genetics to clinical features. Italian J Pediatrics. 40:77. custom designed, high density gene-focused array, aCGH Maclachlan A, Watson SP, Morgan NV. 2017. Inherited
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  • 2020.03.23.20041467V1.Full.Pdf

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  • Chronic Thrombocytopenia As the Initial Manifestation of STIM1

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  • The Role of Genetic Mutations in Gene NBEAL2 in Gray Platelet Syndrome

    The Role of Genetic Mutations in Gene NBEAL2 in Gray Platelet Syndrome

    ARC Journal of Hematology Volume 5, Issue 1, 2020, PP 1-4 www.arcjournals.org The Role of Genetic Mutations in Gene NBEAL2 in Gray Platelet Syndrome Shahin Asadi* Medical Genetics-Harvard University, Director of the Division of Medical Genetics and Molecular Optogenetic Research, Division of Medical Genetics and Molecular Pathology Research, Harvard University, Boston Children's Hospital *Corresponding Author: Shahin Asadi, Medical Genetics-Harvard University. Director of the Division of Medical Genetics and Molecular Optogenetic Research. Division of Medical Genetics and Molecular Pathology Research, Harvard University, Boston Children's Hospital, Email: [email protected] Abstract : Gray platelet syndrome (GPS) is a rare inherited bleeding disorder characterized by macro thrombocytopenia , myelofibrosis, splenomegaly and typical gray appearance of platelets on Wright stained peripheral blood smear. GPS is caused by mutations in the NBEAL2 gene. Absence or marked reduction of alpha -granules in platelets underlies the disorder. Alpha-granules are the most abundant vesicles in platelets and store proteins that promote platelet adhesiveness and wound healing when secreted during platelet activation. Keywords: Gray Platelet Syndrome, Hematology Disorder, NBEAL2 gene. 1. OVERVIEW OF GRAY PLATELET SYNDROME Gray platelet syndrome is a bleeding disorder associated with abnormal platelets that are involved in blood clotting. The skin of people with this syndrome is easily bruised and may increase the risk of nasal bleeding [1]. 2. CLINICAL SIGNS AND SYMPTOMS OF GRAY PLATELET SYNDROME Patients with GD may also experience abnormal or severe bleeding after surgery, dental work or minor skin damage. Women with gray platelet Figure1: Schematic view of the cellular structure of syndrome often experience irregular periods blood platelets (menorrhagia) of menstruation.
  • Blueprint Genetics Bleeding Disorder/Coagulopathy Panel

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