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UNIVERSITY OF MINNESOTA PHYSICIANS OUTREACH LABS Submit this form along with the appropriate Molecular requisition (Molecular Diagnostics or MOLECULAR DIAGNOSTICS (612) 273-8445 Molecular NGS Oncology). DATE: TIME COLLECTED: PCU/CLINIC: AM PM PATIENT IDENTIFICATION DIAGNOSIS (Dx) / DIAGNOSIS CODES (ICD-9) - OUTPATIENTS ONLY SPECIMEN TYPE: o Blood (1) (2) (3) (4) PLEASE COLLECT 5-10CC IN ACD-A OR EDTA TUBE ORDERING PHYSICIAN NAME AND PHONE NUMBER: Tests can be ordered as a full panel, or by individual gene(s). Please contact the genetic counselor with any questions at 612-624-8948 or by pager at 612-899-3291. _______________________________________________ Test Ordered- EPIC: Next generation sequencing(Next Gen) Sunquest: NGS FBN1 Connective tissue Asphyxiating thoracic dystrophy Cranioectodermal dysplasia 2 disorders Full panel WDR35 IFT80 Achondrogenesis DYNC2H1 Craniolenticulosutural dysplasia Full panel TTC21B SEC23A SLC26A2 WDR19 Craniosynostosis TRIP11 Atelosteogenesis Full panel COL2A1 Full panel FGFR2 Achondroplasia SLC26A2 IL11RA FGFR3 FLNB CYP26B1 Acrocapitofemoral dysplasia Brachydactyly TWIST1 IHH Full panel MSX2 Acrodysostosis GDF5 FGFR1 Full panel BMP2 FGFR3 PRKAR1A PTHLH PDE4D Brachyolmia Cutis laxa Acrofacial dysostosis Full panel Full panel Full panel PAPSS2 ATP6V0A2 SF3B4 TRPV4 EFEMP2 DHODH Campomelic dysplasia with autosomal PYCR1 Acromesomelic dysplasia sex reversal ALDH18A1 Full panel SOX9 GDF5 Camurati-Engelmann disease De la Chapelle dysplasia NPR2 TGFB1 SLC26A2 Alport syndrome Cenani-Lenz syndactyly syndrome Full panel DesBuquois syndrome COL4A3 LRP4 CANT1 COL4A4 COL4A5 Chondrocalcinosis Diaphanospondylodysostosis Aortopathy ANKH BMPER Full panel MYH11 Chondrodysplasia Diaphyseal medullary stenosis with ACTA2 Full panel malignant fibrous histiocytoma MYLK IMPAD1 MTAP SLC2A10 PTH1R FBN2 BMPR1B Diastrophic dysplasia COL5A2 SLC26A2 COL5A1 Cleidocranial dysplasia Dyssegmental dysplasia, Silverman- COL3A1 RUNX2 Handmaker type CBS HSPG2 TGFBR1 Craniodiaphyseal dysplasia, autosomal TGFBR2 dominant Ectopia lentis et pupillae SMAD3 SOST ADAMTSL4 4/1/2014 Version 1 Metaphyseal anadysplasia Osteopoikilosis Ehlers Danlos syndrome Full panel LEMD3 Full panel MMP13 Paget disease, juvenile FLNA MMP9 TNFRSF11B FKBP14 Metaphyseal chondrodysplasia Polydactyly, preaxial type II CHST14 Full panel LMBR1 B4GALT7 PTH1R Pycnodysostosis B3GALT6 COL10A1 CTSK COL5A2 Metaphyseal dysplasia with maxillary Raine syndrome COL5A1 hypoplasia with or without FAM20C COL1A1 brachydactyly RoBinow syndrome COL3A1 RUNX2 Full panel PLOD1 Mirror-image polydactyly WNT5A COL1A2 MIPOL1 ROR2 ADAMTS2 Multicentric carpotarsal osteolysis SchneckenBecken dysplasia SLC39A13 syndrome SLC35D1 Eiken syndrome MAFB Short riB-polydactyly syndrome PTH1R Multicentric osteolysis, nodulosis, and Full panel FiBrodysplasia ossificans progressiva arthropathy NEK1 Full panel MMP2 DYNC2H1 ACVR1 Multiple epiphyseal dysplasia WDR35 BMP4 Full panel Small patella syndrome Geleophysic dysplasia COMP TBX4 ADAMTSL2 COL9A2 Split hand/foot malformation frontonasal dysplasia COL9A3 Full panel Full panel SLC26A2 SHFM1 ALX3 MATN3 DLX5 ALX4 COL9A1 WNT10B ALX1 Multiple pterygium syndrome TP63 HEM skeletal dysplasia CHRNG Spondylo-megaepiphyseal-metaphyseal LBR Omodysplasia dysplasia Hereditary multiple exostoses GPC6 Full panel Osteogenesis imperfecta NKX3-2 EXT1 Full panel Spondylocarpotarsal synostosis EXT2 COL1A1 syndrome Hypertrophic osteoarthropathy, COL1A2 primary, autosomal recessive 2 PPIB SCT SLCO2A1 IFITM5 Spondylocostal dysostosis Langer mesomelic dysplasia SERPINF1 SHOX CRTAP Full panel Laron dwarfism LEPRE1 DLL3 GHR SERPINH1 MESP2 Leiomyomatosis, diffuse, with Alport FKBP10 LFNG syndrome SP7 HES7 COL4A6 BMP1 Spondyloenchondrodysplasia Leri-Weill dyschondrosteosis Osteopathia striata with cranial sclerosis SHOX AMER1 ACP5 Loeys-Dietz syndrome Osteopetrosis Spondyloepimetaphyseal dysplasia Full panel Full panel TGFBR1 CLCN7 Full panel TGFBR2 TCIRG1 ACAN SMAD3 TNFSF11 KIF22 TGFB2 CA2 MMP13 TGFBR1 OSTM1 TRAPPC2 TGFBR2 PLEKHM1 WISP3 Marfan syndrome TNFRSF11A CHST3 FBN1 SNX10 DDR2 B3GALT6 4/1/2014 Version 1 Stickler syndrome AKR1C2 Kallmann syndrome 1 Full panel 17-alpha-hydroxylase/17,20-lyase KAL1 COL2A1 deficiency Leydig cell hypoplasia with COL11A1 CYP17A1 pseudohermaphroditism COL11A2 Adrenal hyperplasia, congenital, due to LHCGR COL9A1 11-beta-hydroxylase deficiency Lipoid adrenal hyperplasia Stuve-Wiedemann syndrome/Schwartz- CYP11B1 Jampel type 2 syndrome STAR Adrenal insufficiency, congenital, with LIFR Mullerian aplasia and hyperandrogenism 46XY sex reversal, partial or complete synpolydactyly CYP11A1 WNT4 HOXD13 PERSISTENT MULLERIAN DUCT Synpolydactyly, 3/3'4, associated with Alpha-thalassemia/mental retardation SYNDROME metacarpal and metatarsal synostoses syndrome FBLN1 ATRX AMH Thanatophoric dysplasia Androgen insensitivity AMHR2 FGFR3 AR Pseudohermaphroditism, male, with Treacher Collins syndrome gynecomastia Antley-Bixler syndrome with genital Full panel HSD17B3 anomalies and disordered TCOF1 steroidogenesis Short riB-polydactyly syndrome POLR1D POR Full panel POLR1C Aromatase deficiency Ulna and fiBula, aBsence of, with sever NEK1 limB deficiency CYP19A1 DYNC2H1 WNT7A Campomelic dysplasia with autosomal WDR35 Van Buchem disease sex reversal Smith Lemli Opitz syndrome SOST SOX9 DHCR7 Weill-Marchesani syndrome CHARGE syndrome Full panel Sudden infant death with dysgenesis of CHD7 ADAMTS10 the testes syndrome ADAMTS17 Cryptorchidism TSPYL1 Full panel Chrondrodysplasia, acromesomelic, with genital anomalies INSL3 BMPR1B RXFP2 Testicular anomalies with or without Disorders of sex Desmosterolosis congenital heart disease development DHCR24 GATA4 Denys-Drash syndrome 3-beta-hydroxysteroid dehydrogenase, type II, deficiency WT1 HSD3B2 Disorders of sex development 46,XY ovotesticular DSD EMX2 FGF9 DMRT1 ZFPM2 46,XY sex reversal Fraser syndrome Full panel Full panel AKR1C4 FRAS1 SRY FREM2 RSPO1 GRIP1 SRY Hypospadias 2, X-linked NR0B1 MAMLD1 NR5A1 Pseudovaginal perineoscrotal hypospadias CBX2 SRD5A2 MAP3K1 IMAGE syndrome DHH CDKN1C 4/1/2014 Version 1 Intellectual AFF2 PHF8 disability NLGN4X Autosomal domimant intellectual IQSEC2 disability RPS6KA3 Full panel IL1RAPL1 SCN8A ARX MBD5 PAK3 CACNG2 GDI1 EPB41L1 ZNF81 ARID1B ARHGEF6 ARID1A TSPAN7 SMARCB1 ACSL4 SMARCA4 RAB39B CTNNB1 AGTR2 DOCK8 ZNF41 ZBTB18 FTSJ1 CDH15 DLG3 KIRREL3 ZDHHC15 SYNGAP1 ZNF674 GRIN2B BRWD3 DYRK1A GRIA3 GRIN1 SYP KIF1A ZNF711 Autosomal recessive intellectual disability KIAA2022 Full panel HSD17B10 FGD1 ANK3 PRSS12 SLC9A6 ST3GAL3 UBE2A ZDHHC9 TRAPPC9 TECR HUWE1 MAN1B1 SMS MED23 UPF3B CRBN CLIC2 CC2D1A KDM5C CC2D1A RAB40AL CRADD SOX3 HERC2 PQBP1 TTI2 SHROOM4 NSUN2 AP1S2 TUSC3 CUL4B DIP2B FOXP1 X-linked Intellectual disaBility Full panel PHF6 FMR1 (sequence) 4/1/2014 Version 1 Aural atresia Camptodactyly-arthropathy- Syndromes TSHZ1 coxa vara-pericarditis syndrome 3M syndrome Auriculocondylar syndrome PRG4 Full panel PLCB4 Carpenter syndrome CUL7 Autoimmune disease, RAB23 OBSL1 syndromic multisystem Cerebellar ataxia, mental CCDC8 ITCH retardation, and dysequiliBrium 3MC syndrome Autoinflammation, syndrome 2 Full panel lipodystrophy, and dermatosis WDR81 MASP1 syndrome Cerebral dysgenesis, COLEC11 PSMB8 neuropathy, ichthyosis, and Aarskog-Scott syndrome Bamforth-Lazarus syndrome palmoplantar keratoderma FGD1 FOXE1 syndrome Abruzzo-Erickson syndrome Bardet Biedl syndrome SNAP29 TBX22 Full panel CHARGE syndrome Adams-Oliver BBS1 CHD7 Full panel BBS10 SEMA3E ARHGAP31 TRIM32 CHILD syndrome DOCK6 BBS12 NSDHL ADULT syndrome MKS1 CHIME syndrome TP63 CEP290 PIGL Aicardi-goutieres syndrome WDPCP Choanal atresia and Full panel SDCCAG8 lymphedema TREX1 BBS2 PTPN14 RNASEH2B ARL6 CK syndrome RNASEH2C BBS4 NSDHL RNASEH2A BBS5 Cleft palate and mental SAMHD1 MKKS retardation ADAR BBS7 SATB2 Alagille syndrome TTC8 CluBfoot, congenital, with or Full panel BBS9 without deficiency of long JAG1 Birk-Barel mental retardation bones and/or mirror-image NOTCH2 dysmorphism syndrome polydactyly Alopecia, neurologic defects, KCNK9 PITX1 and endocrinopathy syndrome Blepharophimosis, epicanthus Cocoon syndrome RBM28 inversus, and ptosis, type 2 CHUK Alpha-thalassemia/mental FOXL2 Coffin-Lowry syndrome retardation syndrome Borjeson-Forssman-Lehmann RPS6KA3 ATRX syndrome Cohen syndrome Angelman syndrome PHF6 VPS13B Full panel Bosley-Salih-Alorainy syndrome Congenital cataracts, facial Methylation analysis HOXA1 dysmorphism, and neuropathy SLC9A6 Bowen-Conradi syndrome UBE3A EMG1 CTDP1 Arthrogryposis Brachydactyly-mental Congenital hypothyroidism Full panel retardation syndrome TPM2 HDAC4 PAX8 TNNI2 Brooke-Spiegler syndrome Cornelia de Lange syndrome MYBPC1 CYLD MYH3 Bruck syndrome 2 Full panel MYH8 PLOD2 NIPBL GLE1 Brunner syndrome SMC1A VPS33B MAOA SMC3 VIPAS39 C syndrome (Opitz RAD21 TNNT3 Trignocephaly) HDAC8 AthaBaskan Brainstem CD96 Cousin syndrome dysgenesis syndrome C-like syndrome HOXA1 ASXL1 TBX15 4/1/2014 Version 1 Cranioectodermal dysplasia EVC2 Hemorrhagic destruction of the Full panel EmBerger syndrome brain, subependymal IFT122 GATA2 calcification, and cataracts WDR35 Encephalopahty, lethal, due to JAM3 IFT43 defective mitochondrial Hennekam lymphangiectasia- WDR19 peroxisomal fission lymphedema syndrome Craniofacial anomalies and DNM1L CCBE1 anterior segment dysgenesis Endocrine- Hereditary hemorrhagic syndrome cereBroosteodysplasia telangiectasia VSX1 ICK Full panel Craniofacial dysmorphism, Feingold syndrome SMAD4 skeletal anomalies, and mental MYCN ENG retardation syndrome MIR17HG ACVRL1 TMCO1 Floating-HarBor
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    2018 Etiologies in Order of Frequency by Category Hereditary Syndromes and Disorders Count CHARGE Syndrome 958 Down syndrome (Trisomy 21 syndrome) 308 Usher I syndrome 252 Stickler syndrome 130 Dandy Walker syndrome 119 Cornelia de Lange 102 Goldenhar syndrome 98 Usher II syndrome 83 Wolf-Hirschhorn syndrome (Trisomy 4p) 68 Trisomy 13 (Trisomy 13-15, Patau syndrome) 60 Pierre-Robin syndrome 57 Moebius syndrome 55 Trisomy 18 (Edwards syndrome) 52 Norrie disease 38 Leber congenital amaurosis 35 Chromosome 18, Ring 18 31 Aicardi syndrome 29 Alstrom syndrome 27 Pfieffer syndrome 27 Treacher Collins syndrome 27 Waardenburg syndrome 27 Marshall syndrome 25 Refsum syndrome 21 Cri du chat syndrome (Chromosome 5p- synd) 16 Bardet-Biedl syndrome (Laurence Moon-Biedl) 15 Hurler syndrome (MPS I-H) 15 Crouzon syndrome (Craniofacial Dysotosis) 13 NF1 - Neurofibromatosis (von Recklinghausen dis) 13 Kniest Dysplasia 12 Turner syndrome 11 Usher III syndrome 10 Cockayne syndrome 9 Apert syndrome/Acrocephalosyndactyly, Type 1 8 Leigh Disease 8 Alport syndrome 6 Monosomy 10p 6 NF2 - Bilateral Acoustic Neurofibromatosis 6 Batten disease 5 Kearns-Sayre syndrome 5 Klippel-Feil sequence 5 Hereditary Syndromes and Disorders Count Prader-Willi 5 Sturge-Weber syndrome 5 Marfan syndrome 3 Hand-Schuller-Christian (Histiocytosis X) 2 Hunter Syndrome (MPS II) 2 Maroteaux-Lamy syndrome (MPS VI) 2 Morquio syndrome (MPS IV-B) 2 Optico-Cochleo-Dentate Degeneration 2 Smith-Lemli-Opitz (SLO) syndrome 2 Wildervanck syndrome 2 Herpes-Zoster (or Hunt) 1 Vogt-Koyanagi-Harada
  • My Beloved Neutrophil Dr Boxer 2014 Neutropenia Family Conference

    My Beloved Neutrophil Dr Boxer 2014 Neutropenia Family Conference

    The Beloved Neutrophil: Its Function in Health and Disease Stem Cell Multipotent Progenitor Myeloid Lymphoid CMP IL-3, SCF, GM-CSF CLP Committed Progenitor MEP GMP GM-CSF, IL-3, SCF EPO TPO G-CSF M-CSF IL-5 IL-3 SCF RBC Platelet Neutrophil Monocyte/ Basophil B-cells Macrophage Eosinophil T-Cells Mast cell NK cells Mature Cell Dendritic cells PRODUCTION AND KINETICS OF NEUTROPHILS CELLS % CELLS TIME Bone Marrow: Myeloblast 1 7 - 9 Mitotic Promyelocyte 4 Days Myelocyte 16 Maturation/ Metamyelocyte 22 3 – 7 Storage Band 30 Days Seg 21 Vascular: Peripheral Blood Seg 2 6 – 12 hours 3 Marginating Pool Apoptosis and ? Tissue clearance by 0 – 3 macrophages days PHAGOCYTOSIS 1. Mobilization 2. Chemotaxis 3. Recognition (Opsonization) 4. Ingestion 5. Degranulation 6. Peroxidation 7. Killing and Digestion 8. Net formation Adhesion: β 2 Integrins ▪ Heterodimer of a and b chain ▪ Tight adhesion, migration, ingestion, co- stimulation of other PMN responses LFA-1 Mac-1 (CR3) p150,95 a2b2 a CD11a CD11b CD11c CD11d b CD18 CD18 CD18 CD18 Cells All PMN, Dendritic Mac, mono, leukocytes mono/mac, PMN, T cell LGL Ligands ICAMs ICAM-1 C3bi, ICAM-3, C3bi other other Fibrinogen other GRANULOCYTE CHEMOATTRACTANTS Chemoattractants Source Activators Lipids PAF Neutrophils C5a, LPS, FMLP Endothelium LTB4 Neutrophils FMLP, C5a, LPS Chemokines (a) IL-8 Monocytes, endothelium LPS, IL-1, TNF, IL-3 other cells Gro a, b, g Monocytes, endothelium IL-1, TNF other cells NAP-2 Activated platelets Platelet activation Others FMLP Bacteria C5a Activation of complement Other Important Receptors on PMNs ñ Pattern recognition receptors – Detect microbes - Toll receptor family - Mannose receptor - bGlucan receptor – fungal cell walls ñ Cytokine receptors – enhance PMN function - G-CSF, GM-CSF - TNF Receptor ñ Opsonin receptors – trigger phagocytosis - FcgRI, II, III - Complement receptors – ñ Mac1/CR3 (CD11b/CD18) – C3bi ñ CR-1 – C3b, C4b, C3bi, C1q, Mannose binding protein From JG Hirsch, J Exp Med 116:827, 1962, with permission.