Klinische FragestellungThrombozytopenien + Thrombozytopathien, hereditäre; Differentialdiagnose
Zusammenfassung
Umfassendes differentialdiagnostisches panel für Thrombozytopenien + Thrombozytopathien mit 6 bzw. zusammen genommen 71 kuratierten Genen gemäß klinischer Verdachtsdiagnose
103,2 kb (Erweitertes Panel: inkl. additional genes)
- EDTA-Blut (3-5 ml)
NGS +
[Sanger]
Genpanel
Ausgewählte Gene
Name | Exon-Länge (bp) | OMIM-G | Referenz-Seq. | Erbgang |
---|---|---|---|---|
GP1BA | 1959 | NM_000173.7 | AD, AR | |
GP1BB | 621 | NM_000407.5 | AD, AR | |
GP9 | 534 | NM_000174.5 | AR | |
ITGA2B | 3120 | NM_000419.5 | AD, AR | |
ITGB3 | 2367 | NM_000212.3 | AD, AR | |
NBEAL2 | 8265 | NM_015175.3 | AR | |
ABCG5 | 1956 | NM_022436.3 | AR | |
ABCG8 | 2022 | NM_022437.3 | AR | |
ACTB | 1128 | NM_001101.5 | AD | |
ACTN1 | 2745 | NM_001130004.2 | AD | |
ACVRL1 | 1512 | NM_000020.3 | AD | |
ANKRD26 | 5133 | NM_014915.3 | AD | |
ANO6 | 2733 | NM_001025356.3 | AR | |
AP3B1 | 3138 | NM_001271769.2 | AR | |
ARPC1B | 1141 | NM_005720.4 | AR | |
BLOC1S3 | 609 | NM_212550.5 | AR | |
BLOC1S6 | 519 | NM_012388.4 | AR | |
CDC42 | 576 | NM_001791.4 | AD | |
CYCS | 318 | NM_018947.6 | AD | |
DIAPH1 | 3819 | NM_005219.5 | AD | |
DTNBP1 | 813 | NM_001271667.2 | AR | |
ETV6 | 1359 | NM_001987.5 | AD | |
FERMT3 | 1992 | NM_031471.6 | AR | |
FLI1 | 1359 | NM_002017.5 | AD, AR | |
FYB1 | 2783 | NM_001243093.2 | AR | |
GATA1 | 1242 | NM_002049.4 | XLR | |
GFI1B | 993 | NM_004188.8 | AD, AR | |
GP6 | 1863 | NM_001083899.2 | AR | |
HOXA11 | 942 | NM_005523.6 | AD | |
HPS1 | 2103 | NM_000195.5 | AR | |
HPS3 | 3015 | NM_032383.5 | AR | |
HPS4 | 2127 | NM_022081.6 | AR | |
HPS5 | 3048 | NM_007216.4 | AR | |
HPS6 | 2328 | NM_024747.6 | AR | |
MECOM | 3351 | NM_001105077.4 | AD | |
MPIG6B | 910 | NM_025260.4 | AR | |
MPL | 1908 | NM_005373.3 | AR, AD | |
MYH9 | 5883 | NM_002473.6 | AD | |
PLA2G4A | 2250 | NM_024420.3 | AR | |
PLAU | 1245 | NM_001145031.3 | AD | |
PRKACG | 1056 | NM_002732.4 | AR | |
RASGRP2 | 1830 | NM_153819.1 | AR | |
RUNX1 | 1443 | NM_001754.5 | AD | |
SLFN14 | 2743 | NM_001129820.2 | AD | |
SRC | 1611 | NM_005417.5 | AD | |
STIM1 | 2058 | NM_003156.4 | AD | |
TBXA2R | 1032 | NM_001060.6 | AD, AR | |
THBD | 1728 | NM_000361.3 | AD | |
THPO | 1062 | NM_000460.4 | AD | |
TUBB1 | 1356 | NM_030773.4 | AD, AR | |
WAS | 1509 | NM_000377.3 | XLR |
Infos zur Erkrankung
Thrombozyten stoppen den Blutfluss unmittelbar nach Verletzungen durch grundlegend verschiedene Mechanismen: Aktivierung, Adhäsion, Aggregation, Sekretion und Förderung der Gerinnung. Die klinischen Komplikationen bei Patienten mit Thrombozyten-Störungen ist sehr unterschiedlich, selbst innerhalb ein und desselben Typs, und reicht von nahezu unbedeutend bis lebensbedrohlich. Bei Thrombozytopenien (z.B. Wiskott-Aldrich-Syndrom) oder Thrombozytopathien (z.B. Bernard-Soulier-Syndrom, Glanzmann-Thrombasthenie) treten die Blutungen im Allgemeinen unmittelbar nach der Verletzung auf, vor allem in der Haut, den Schleimhäuten, der Nase, dem Magen-Darm-Trakt und den Harnwegen. Im Allgemeinen sind die Gelenke und Muskeln von den Blutungen nicht betroffen. Angeborene Erkrankungen sind selten und können mitunter nur schwer von erworbenen Störungen differenziert werden, wobei letztere in der klinischen Praxis viel häufiger vorkommen. Die Differentialdiagnose ist oft komplex. Eine lebenslange Blutungsneigung kann auf eine angeborene Thrombozyten-Funktionsstörung hindeuten, die oft in der Kindheit erkannt wird, aber ein Auftreten im Erwachsenenalter schließt einen angeborenen Defekt nicht aus. Erbliche Thrombozyten-Störungen umfassen eine heterogene Gruppe von >60 seltenen Krankheiten, die durch Mutationen in >70 Genen verursacht werden. Die Vererbungsmuster umfassen autosomal dominante und rezessive sowie X-chromosomale Transmission. Die DNA-diagnostische Ausbeute hängt stark von der Qualität der klinischen Phänotypisierung ab und liegt bei Thrombozytopenien bei <25 % und bei Thrombozytopathien bei ~40 %. Daher schließt ein negatives molekulargenetisches Testergebnis die klinische Diagnose nicht aus.
Referenzen: 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
- 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)
- AD
- AR
- XLR
- Multiple OMIM-Ps
Bioinformatik und klinische Interpretation
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