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Interdisciplinary CompetenceMolecular Diagnostics
Know how in the analysis of genetic material.
For the benefit of patients.

IllnessThrombocytopenias + thrombocytopathies, hereditary; differential diagnosis

Summary

Short information

Comprehensive differential diagnostic panel for Thrombocytopenias + thrombocytopathies containing 6 core candidate genes and altogether 71 curated genes according to the clinical signs

ID
TP5445
Number of genes
53 Accredited laboratory test
Examined sequence length
16,9 kb (Core-/Core-canditate-Genes)
117,7 kb (Extended panel: incl. additional genes)
Analysis Duration
on request
Material
  • EDTA-anticoagulated blood (3-5 ml)
Diagnostic indications

NGS +

[Sanger]

 

Gene panel

Selected genes

NameExon Length (bp)OMIM-GReferenz-Seq.Heredity
GP1BA1959NM_000173.7AD, AR
GP1BB621NM_000407.5AD, AR
GP9534NM_000174.5AR
ITGA2B3120NM_000419.5AD, AR
ITGB32367NM_000212.3AD, AR
NBEAL28265NM_015175.3AR
ABCG51956NM_022436.3AR
ABCG82022NM_022437.3AR
ACTB1128NM_001101.5AD
ACTN12745NM_001130004.2AD
ACVRL11512NM_000020.3AD
ANKRD265133NM_014915.3AD
ANO62733NM_001025356.3AR
AP3B13138NM_001271769.2AR
ARPC1B1141NM_005720.4AR
BLOC1S3609NM_212550.5AR
BLOC1S6519NM_012388.4AR
CDC42576NM_001791.4AD
CYCS318NM_018947.6AD
DIAPH13819NM_005219.5AD
DTNBP1813NM_001271667.2AR
ETV61359NM_001987.5AD
FERMT31992NM_031471.6AR
FLI11359NM_002017.5AD, AR
FYB12783NM_001243093.2AR
GATA11242NM_002049.4XLR
GFI1B993NM_004188.8AD, AR
GP61863NM_001083899.2AR
HOXA11942NM_005523.6AD
HPS12103NM_000195.5AR
HPS33015NM_032383.5AR
HPS42127NM_022081.6AR
HPS53048NM_007216.4AR
HPS62328NM_024747.6AR
MECOM3351NM_001105077.4AD
MPIG6B910NM_025260.4AR
MPL1908NM_005373.3AR, AD
MYH95883NM_002473.6AD
PLA2G4A2250NM_024420.3AR
PLAU1245NM_001145031.3AD
PRKACG1056NM_002732.4AR
PTPN111782NM_002834.5AD
RASGRP21830NM_153819.1AR
RUNX11443NM_001754.5AD
SLFN142743NM_001129820.2AD
SRC1611NM_005417.5AD
STIM12058NM_003156.4AD
TBXA2R1032NM_001060.6AD, AR
THBD1728NM_000361.3AD
THPO1062NM_000460.4AD
TNXB12729NM_019105.8AR
TUBB11356NM_030773.4AD, AR
WAS1509NM_000377.3XLR

Informations about the disease

Clinical Comment

Platelets stop the blood flow immediately after injury through fundamentally different mechanisms: activation, adhesion, aggregation, secretion and promotion of coagulation. The clinical complications in patients with thrombocyte disorders varies widely, even within the same type, ranging from almost insignificant to life-threatening. In thrombocytopenias (e.g. Wiskott-Aldrich syndrome) or thrombocytopathies (e.g. Bernard-Soulier syndrome, Glanzmann thrombasthenia), bleeding generally occurs immediately after injury, especially in the skin, mucous membranes, nose, gastrointestinal tract and urinary tract. Generally, the joints and muscles are not affected by the bleeding. Congenital disorders are rare and can easily be confused with acquired disorders, the latter being much more common in clinical practice. Thus the differential diagnosis is often complex. A lifelong tendency to bleed may indicate a congenital platelet dysfunction, often recognised in childhood, but occurrence in adulthood does not rule out a congenital defect. The hereditary platelet disorders comprise a heterogeneous group of >60 rare diseases caused by mutations in >70 genes. Inheritance patterns include autosomal dominant and recessive as well as X-linked transmission. The DNA diagnostic yield is highly dependent on the quality of clinical phenotyping and ranging <25% for thrombocytopenias and around 40% for thrombocytopathies. Therefore, a negative molecular genetic test result does not exclude the clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK1178/

https://www.ncbi.nlm.nih.gov/books/NBK7014/

https://www.mdpi.com/1422-0067/22/9/4521/htm

 

Synonyms
  • Allelic: Alzheimer disease, late-onset, susceptibility to (PLAU)
  • Allelic: Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to (TRPM7)
  • Allelic: Anemia, XL, with/without neutropenia and/or platelet abnormalities (GATA1)
  • Allelic: Cardiac valvular dysplasia, XL (FLNA)
  • Allelic: Colon cancer, advanced, somatic (SRC)
  • Allelic: Deafness, AD 17 (MYH9)
  • Allelic: Erythrokeratodermia variabilis et progressiva 4 (KDSR)
  • Allelic: FG syndrome 2 (FLNA)
  • Allelic: Frontometaphyseal dysplasia 1 (FLNA)
  • Allelic: Hemolytic uremic syndrome, atypical, susceptibility to, 6 (THBD)
  • Allelic: Heterotopia, periventricular, 1 (FLNA)
  • Allelic: Leukemia, acute myeloid (RUNX1)
  • Allelic: Leukemia, acute myeloid, somatic (ETV6)
  • Allelic: Leukemia, megakaryoblastic, with/-out Down syndrome, somatic (GATA1)
  • Allelic: Melnick-Needles syndrome (FLNA)
  • Allelic: Metachondromatosis (PTPN11)
  • Allelic: Myelofibrosis with myeloid metaplasia, somatic (MPL)
  • Allelic: Myocardial infarction, susceptibility to (ITGB3)
  • Allelic: Neutropenia, severe congenital, XL (WASP)
  • Allelic: Nonarteritic anterior ischemic optic neuropathy, susceptibility to (GP1BA)
  • Allelic: Otopalatodigital syndrome, type I (FLNA)
  • Allelic: Otopalatodigital syndrome, type II (FLNA)
  • Allelic: Purpura, posttransfusion (ITGB3)
  • Allelic: Seizures, cortical blindness, microcephaly syndrome (DIAPH1)
  • Allelic: Terminal osseous dysplasia (FLNA)
  • Allelic: Thrombocytopenia, neonatal alloimmune (ITGB3)
  • Allelic: Thrombocytopenia, neonatal alloimmune, BAK antigen related (ITGA2B)
  • Allelic: Vesicoureteral reflux 8 (TNXB)
  • Allelic: Wiskott-Aldrich syndrome (WASP)
  • Bernard-Soulier syndrome, type B (GP1BB)
  • Bernard-Soulier syndrome, type C (GP9)
  • Bernard-Soulier syndrome, types A1 [AR] + A2 [AD] (GP1BA)
  • Bleeding disorder, platelet-type, 1 [Bernard-Soulier syndrome] (GP9, GP1BA, GP1BB)
  • Bleeding disorder, platelet-type, 11 (GP6)
  • Bleeding disorder, platelet-type, 12 (PTGS1)
  • Bleeding disorder, platelet-type, 13, susceptibility to (TBXA2R)
  • Bleeding disorder, platelet-type, 15 (ACTN1)
  • Bleeding disorder, platelet-type, 16, AD (ITGA2B)
  • Bleeding disorder, platelet-type, 17 (GFI1B)
  • Bleeding disorder, platelet-type, 18 (RASGRP)
  • Bleeding disorder, platelet-type, 19 (PRKACG)
  • Bleeding disorder, platelet-type, 20 (SLFN14)
  • Bleeding disorder, platelet-type, 21 (FLI1)
  • Bleeding disorder, platelet-type, 24, AD (ITGB3)
  • Bleeding disorder, platelet-type, 7 [Scott syndrome] (ANO6)
  • Bleeding disorder, platelet-type, 8 (P2RY12)
  • Congenital short bowel syndrome (FLNA)
  • Deafness, AD 1, with/-out thrombocytopenia (DIAPH1)
  • Dominant macrothrombocytopenia, mild bleeding, disrupted cytoskeleton remodeling [lit.] (TPM4)
  • Ehlers-Danlos syndrome due to tenascin X deficiency [panelapp] (TNXB)
  • Ehlers-Danlos syndrome, classic-like, 1 (TNXB)
  • Ehlers-Danlos syndrome, musculocontractural type 1 (CHST14)
  • Gastrointestinal ulceration, recurrent, with dysfunctional platelets (PLA2G4A)
  • Ghosal hematodiaphyseal syndrome (TBXAS1)
  • Giant platelet disorder, isolated (GP1BB)
  • Glanzmann thrombasthenia (ITGA2B, ITGB3)
  • Gray platelet syndrome (NBEAL2)
  • Hemophagocytic lymphohistiocytosis, familial, 3 (UNC13D)
  • Hemophagocytic lymphohistiocytosis, familial, 5, with/-out microvillus inclusion disease (STXBP2)
  • Hermansky-Pudlak syndrome 1, 3, 4, 5, 6 (HPS1, HPS3, HPS4, HPS5, HPS6)
  • Hermansky-Pudlak syndrome 10 (AP3D1)
  • Hermansky-Pudlak syndrome 2 (AP3B1)
  • Hermansky-Pudlak syndrome 7 (DTNBP1)
  • Hermansky-Pudlak syndrome 8, 9 (BLOC1S3, BLOC1S6)
  • Immunodeficiency 71 with inflammatory disease + congenital thrombocytopenia (ARPC1B)
  • Inherited Thrombocytopenia assiciated with mutation of UDP-Galactose-4-Epimerase (GALE)
  • Intestinal pseudoobstruction, neuronal (FLNA)
  • LEOPARD syndrome 1 (PTPN11)
  • Leukocyte adhesion deficiency, type III (FERMT3)
  • Macrothrombocytopenia + granulocyte incl. with/-out nephritis/sensorineural hearing loss (MYH9)
  • Macrothrombocytopenia [panelapp] (TRPM7)
  • Macrothrombocytopenia, AD, TUBB1-related (TUBB1)
  • Myopathy associated with thrombocytopenia [panelapp] (GNE)
  • Noonan syndrome 1 (PTPN11)
  • Platelet disorder, familial, with associated myeloid malignancy (RUNX1)
  • Purinergic receptor P2X, ligand-gated ion channel, 1 deficiency (P2RX1)
  • Quebec platelet disorder (PLAU)
  • Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 (HOXA11)
  • Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 (MECOM)
  • Recessive severe thrombocytopenia with progression to marrow fibrosis at young age [panelapp] (KDSR)
  • Significant bruising/haematomas [panelapp] (TNXB)
  • Sitosterolemia 1 (ABCG8)
  • Sitosterolemia 2 (ABCG5)
  • Stormorken syndrome [YORK platelet syndrome] (STIM1)
  • Takenouchi-Kosaki syndrome (CDC42)
  • Telangiectasia, hereditary hemorrhagic, type 1 (ENG)
  • Telangiectasia, hereditary hemorrhagic, type 2 (ACVRL1)
  • Thrombocythemia 1 (THPO)
  • Thrombocythemia 2 (MPL)
  • Thrombocytopenia 2 (ANKRD26)
  • Thrombocytopenia 3 (FYB1)
  • Thrombocytopenia 4 (CYCS)
  • Thrombocytopenia 5 (ETV6)
  • Thrombocytopenia 6 (SRC)
  • Thrombocytopenia with beta-thalassemia, XL (GATA1)
  • Thrombocytopenia, AD, 7 (IKZF5)
  • Thrombocytopenia, XL (WASP)
  • Thrombocytopenia, XL, intermittent (WASP)
  • Thrombocytopenia, XL, with/-out dyserythropoietic anemia (GATA1)
  • Thrombocytopenia, anemia + myelofibrosis (MPIG6B)
  • Thrombocytopenia, congenital amegakaryocytic (MPL)
  • Thrombocytopenia, neonatal alloimmune (ITGB3)
  • Thrombocytopenia-absent radius syndrome (RBM8A)
  • Thrombophilia due to thrombomodulin defect (THBD)
  • Thrombotic thrombocytopenic purpura, hereditary (ADAMTS13)
  • von Willebrand disease, platelet-type (GP1BA)
  • von Willebrand disease, type 1 (VWF)
  • von Willebrand disease, type 3 (VWF)
  • von Willebrand disease, types 2A, 2B, 2M + 2N (VWF)
Heredity, heredity patterns etc.
  • AD
  • AR
  • XLR
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code

Bioinformatics and clinical interpretation

No text defined