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Genes Included in the Next-Generation Sequencing Panel for Inherited Cytopenias

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Gene list version 1 – May 2019 Genes included in the next-generation sequencing panel for inherited cytopenias. Disease Gene Notes Inheritance Dyskeratosis congenita Dyskeratosis congenita TERT AD, AR Dyskeratosis congenita TERC AD Dyskeratosis congenita TINF2 AD Dyskeratosis congenita RTEL1 AD, AR Dyskeratosis congenita DKC1 XLR Dyskeratosis congenita NOP10 NOLA3 AR Dyskeratosis congenita NHP2 NOLA2 AR Dyskeratosis congenita WRAP53 AR Dyskeratosis congenita CTC1 AR Dyskeratosis congenita PARN AR Dyskeratosis congenita ACD AD, AR Fanconi anemia Fanconi anemia / Familial breast FANCA AR cancer Fanconi anemia FANCB Deletions "common" in FANC genes XLR? Fanconi anemia FANCC Does not cover 21q22.11-q22.13 monosomy AR Fanconi anemia AR/ AD inheritance BRCA2 FANCD1 AR for Wilms tumor, breast cancer, medulloblastoma, prostate cancer Fanconi anemia FANCD2 AR Fanconi anemia FANCE AR Fanconi anemia FANCF AR Fanconi anemia FANCG XRCC9 AR Fanconi anemia FANCI AR Fanconi anemia / AD Familial BRIP1 FANCJ AR breast cancer Fanconi anemia FANCL AR Fanconi anemia FANCM FANCM mutations in combination with FANCA? AR Gene list version 1 – May 2019 Fanconi anemia / AD Familial breast PALB2 FANCN AR cancer Fanconi anemia / Familial breast RAD51C FANCO AR cancer Fanconi anemia / Familial breast SLX4 FANCP AR cancer, rare Fanconi anemia / Xeroderma ERCC4 FANCQ / XPF AR pigmentosum, group F Fanconi anemia XRCC2 FANCR AR Fanconi anemia, complementation UBE2T AR group T Fanconi anemia BRCA1 AR DCML/MonoMAC/ familial GATA2 AD AA/MDS/AML/CMML IRF8 deficiency IRF8 AD, AR HYOU1 deficiency (SCN+DC HYOU1 chr11: 118922614 C>G, p.A419P and AR deficiency) chr11:118924936 A>G, p.Y231H DADA2 / Polyarteritis CECR1 AR nodosa/Sneddon syndrome Bone marrow failure ERCC6L2 deficiency / Bone marrow ERCC6L2 AR failure syndrome Congenital Bone Marrow Failure SRP72 AD BMF/AA/MDS and deafness Shwachman syndrome, AR / SBDS AR, AD Aplastic anemia, susceptibility to, AD Thrombocytopenia Wiskott-Aldrich syndrome / WAS XLR Thrombocytopenia / Neutropenia, severe congenital Thrombocytopenia 4 CYCS AD Anemia / Leukemia, GATA1 XLR megakaryoblastic, with or without Down syndrome, somatic / Thrombocytopenia with beta- thalassemia / Thrombocytopenia, Gene list version 1 – May 2019 X-linked, with or without dyserythropoietic anemia Amegakaryocytic TP with radio- HOXA11 AD ulnar synostosis Thrombocytopenia 2 ANKRD26 reduced platelet alpha granules AD Bleeding disorder, platelet-type, 16 ITGB3 AD, AR / Glanzmann thrombasthenia /Thrombocytopenia, neonatal alloimmune /Purpura, posttransfusion Familial AA / Thrombocytopenia, MPL AD, Smu, AR congenital amegakaryocytic Familial platelet disorder /AML RUNX1 AD (FPD/AML) Bleeding disorder, platelet-type, 17 GFI1B almost absent platelet alpha granules AD Thrombocythemia 1 THPO AD Thrombocytopenia with absent RBM8A Thrombocytopenias with normal-sized platelets AR radii / Does not cover 1q21.1del Thrombocytopenia, fair complexion SBF2 c.659C>G (p.Thr220Arg) in the SBF2 (also known AR as MTMR13) Bernard-Soulier / von Willebrand GP1BA Thrombocytopenias with large/giant platelets / AD, AR disease, platelet-type Platelet-type vWD possible Bernard-Soulier syndrome, type B / GP1BB giGeorge/VC phenotype possible AR Giant platelet disorder, isolated Bernard-Soulier syndrome, type C GP9 AR Paris-Trousseau FLI1 usually 11q23ter, giant platelet alpha granules / AD hemizygous loss of FLI1 Grey platelet sdr NBEAL2 no alpha granules AR Macrothrombocytopenia and MYH9 AD progressive sensorineural deafness / Epstein syndrome /Fechtner syndrome / May-Hegglin anomaly /Sebastian syndrome Bleeding disorder, platelet-type, 16 ITGA2B AD, AR / Glanzmann thrombasthenia /Thrombocytopenia, neonatal alloimmune, BAK antigen related TP with sitosterolenemia ABCG5 AR Gene list version 1 – May 2019 Sitosterolemia ABCG8 AR Bleeding disorder, platelet-type, 15 ACTN1 AD Filaminopathies etc. FLNA large alpha granules XLD, XLR Macrothrombocytopenia, TUBB1 AD Bleeding disorder, platelet-type, 19 PRKACG AR Quebec platelet disorder PLAU TP in some, bleeding AD Thrombocytopaenia, small-platelet FYB Thrombocytopenias with small platelets AR AML AML CEBPA AD Thrombocytopenia 5 / AML, ETV6 AD somatic Bloom syndrome BLM RECQL3 AR STK4 deficiency / T-cell STK4 MST1 AR immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations Reticular dysgenesis AK2 AR Cartilage-hair hypoplasia RMRP AR Neutropenia Severe congenital/ cyclic ELANE AD neutropenia Poikiloderma with neutropenia USB1 C16ORF57 AR Severe congenital neutropenia GFI1 AD Neutropenia, severe congenital 3 HAX1 AR severe congenital neutropenia VPS45 AR (SCN)+ myelofibrosis Dursun syndrome / Neutropenia, G6PC3 AR severe congenital Neutropenia, severe congenital JAGN1 AR Barth syndrome TAZ neutropenia XLR Neutrophilia, hereditary CSF3R AD Cohen syndrome VPS13B COH1 AR Gene list version 1 – May 2019 WHIM syndrome CXCR4 AD Intrinsic factor deficiency GIF AR Transcobalamin II deficiency TCN2 AR Diamond-Blackfan anemia Diamond-Blackfan anemia RPS19 AD Diamond-Blackfan anemia RPS26 possibly with mandibulofacial dysostosis AD Diamond-Blackfan anemia RPL5 AD Diamond-Blackfan anemia RPL11 AD Diamond-Blackfan anemia RPS24 AD Diamond-Blackfan anemia RPS17 AD Diamond-Blackfan anemia TSR2 with mandibulofacial dysostosis XLR Diamond-Blackfan anemia RPS7 AD Diamond-Blackfan anemia RPL35A AD Diamond-Blackfan anemia RPS10 AD Diamond-Blackfan anemia RPS28 with mandibulofacial dysostosis AD Diamond-Blackfan anemia RPS29 AD Diamond-Blackfan anemia RPL15 AD Dyserythropoietic anemia Dyserythropoietic anemia, SEC23B CDAN2 AR congenital, type II Dyserythropoietic anemia, CDAN1 CDAN1a AR congenital, type Ia Dyserythropoietic anemia, C15orf41 CDAN1B AR congenital, type Ib Dyserythropoietic anemia, KLF1 AD congenital, type IV Majeed syndrome LPIN2 multifocal osteomyelitis and congenital AR dyserythropoietic anemia Exocrine pancreatic insufficiency, COX4I2 AR dyserythropoietic anemia, and calvarial hyperostosis Sideroblastic anemias Gene list version 1 – May 2019 Congenital sideroblastic anemias ALAS2 Does not cover mitochondrial PMPS/CSA XLR (CSA) / Protoporphyria, erythropoietic XLD Myopathy, lactic acidosis, and YARS2 AR sideroblastic anemia 2 Mitochondrial myopathy and PUS1 AR sideroblastic anemia 1 Anemia, sideroblastic, pyridoxine- GLRX5 AR refractory Anemia, sideroblastic, pyridoxine- SLC25A38 AR refractory Sideroblastic anemia with B-cell TRNT1 AR immunodeficiency, periodic fevers, and developmental delay Anemia, sideroblastic, with ataxia ABCB7 XLR Thiamine-responsive megaloblastic SLC19A2 AR anemia syndrome Congenital sideroblastic anemias HSPA9 http://m.bloodjournal.org/content/126/25/2734 AD, AR (CSA) new gene Hemolytic anemia Hemolytic anemia due to G6PD G6PD XLR? deficiency Pyruvate kinase deficiency / PKLR AR hemolytic anemia Cryohydrocytosis etc. SLC4A1 AD Hemolytic anemia, nonspherocytic, GPI AR due to glucose phosphate isomerase deficiency Phosphoglycerate kinase 1 PGK1 XLR deficiency Anemia, hemolytic, due to UMPH1 NT5C3A AR deficiency Hemolytic anemia due to adenylate AK1 AR kinase deficiency Hemolytic anemia due to HK1 AR hexokinase deficiency / neuropathy Gene list version 1 – May 2019 Hemolytic anemia due to TPI1 AR triosephosphate isomerase deficiency Hemolytic anemia due to GSS AR glutathione synthetase deficiency Hereditary nonspherocytic ADA GOF suspected Smo, AR hemolytic anemias Hemolytic anemia due to PFKL AR? phosphofructokinase deficiency Hemolytic anemia due to GSR AR? glutathione reductase deficiency Glycogen storage disease Metabolic myopathy / haemolysis / ALDOA hemolytic anemia AR Glycogen storage disease XII Glycogen storage disease Ib SLC37A4 hypoglycemia, hyperlactic acidemia, colitis AR Glycogen storage disease VII PFKM AR Other platelet alpha-granule deficiencies Arthrogryposis, renal dysfunction, VPS33B AR and cholestasis 1 Specific granule deficiency CEBPE with specific granule deficiency AR Storage diseases with severe hematological phenotype Gaucher disease GBA AR Gaucher disease, atypical / PSAP Gaucher AR Combined SAP deficiency / Krabbe disease, atypical / Metachromatic leukodystrophy due to SAP-b deficiency Cholesteryl ester storage disease / LIPA Wolman/familial HLH; CESD AR Wolman disease Other disorders with splenomegaly w/o PIDD Hereditary hemorrhagic ENG AD telangiectasia Telangiectasia, hereditary ACVRL1 AD hemorrhagic, type 2 Gene list version 1 – May 2019 Juvenile polyposis/hereditary SMAD4 MADH4/ also juvenile polyposis AD hemorrhagic telangiectasia syndrome / Myhre syndrome / Polyposis, juvenile intestinal Thalassemias Thalassemias etc. HBA2 alpha, deletions common AD Thalassemias etc. HBA1 alpha, deletions common AD Thalassemias etc. HBB beta, deletions common AD Spherocytosis Hereditary spherocytoses ANK1 AD Spherocytosis, type 2 SPTB AD Spherocytosis, type 3 SPTA1 AR Spherocytosis, type 5 EPB42 AR Hemochromatosis Hemochromatosis HFE AR, AD Hemochromatosis, type 2A HFE2 AR Hemochromatosis, type 2B HAMP AR Hemochromatosis, type 3 TFR2 AR Hemochromatosis, type 4 SLC40A1 AD Cystic fibrosis CFTR AR Familial Mediterranean fever MEFV AD, AR Wilson disease ATP7B AR Niemann-Pick types A-D SMPD1 type A & B AR Niemann-Pick types A-D NPC1 type C1 & D AR Niemann-Pick types A-D NPC2 type C2 AR Mucoplysaccharidoses Mucoplysaccharidoses IDUA AR Mucopolysaccharidosis II IDS XLR Mucopolysaccharidisis type IIIA SGSH AR (Sanfilippo A) Mucopolysaccharidosis type IIIB NAGLU AR (Sanfilippo B) Gene list version 1 – May 2019 Mucopolysaccharidosis type IIIC HGSNAT AR (Sanfilippo C) Mucopolysaccharidosis
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  • Mutation of the ABCA1 Gene in Hypoalphalipoproteinemia with Corneal Lipidosis

    Mutation of the ABCA1 Gene in Hypoalphalipoproteinemia with Corneal Lipidosis

    4600/366J Hum Genet (2002) 47:366–369 N. Matsuda et al.: © Jpn EGF Soc receptor Hum Genet and osteoblastic and Springer-Verlag differentiation 2002 SHORT COMMUNICATION Jun Ishii · Makoto Nagano · Takeshi Kujiraoka Mitsuaki Ishihara · Tohru Egashira · Daisuke Takada Masahiro Tsuji · Hiroaki Hattori · Mitsuru Emi Clinical variant of Tangier disease in Japan: mutation of the ABCA1 gene in hypoalphalipoproteinemia with corneal lipidosis Received: March 1, 2002 / Accepted: March 15, 2002 Abstract Despite progress in molecular characterization, hypoalphalipoproteinemia syndromes have hampered their specific diagnoses of disorders belonging to a group of in- classification into distinct disease entities. From a clinical herited hypoalphalipoproteinemias, i.e., apolipoprotein AI standpoint, the term “inherited hypoalphalipoproteinemia” deficiency, lecithin-cholesterol acyltransferase deficiency, can apply to apolipoprotein AI (apoAI) deficiency, lecithin- Tangier disease (TD), and familial high-density lipoprotein cholesterol acyltransferase (LCAT) deficiency, Tangier (HDL) deficiency, remain difficult on a purely clinical basis. disease (TD), or so-called familial high-density lipoprotein Several TD patients were recently found to be homozygous (HDL) deficiency (Assmann et al. 1995). Despite some for mutations in the ABCA1 gene. We have documented progress in molecular characterization, specific diagnoses of here a clinical variant of TD in a Japanese patient who these disorders remain difficult because of their phenotypic manifested corneal lipidosis and premature coronary artery spectra overlap and because the penetrance of some symp- disease as well as an almost complete absence of HDL- toms is age related. cholesterol, by identifying a novel homozygous ABCA1 Mutation in ABCA1, a gene mapping to 9q31 and encod- mutation (R1680W). We propose that patients with ap- ing an ATP-binding cassette transporter, confers suscepti- parently isolated HDL deficiency who are found to carry bility to TD, a recessive disease (Bodzioch et al.