Page 427 - Hematology_ Basic Principles and Practice ( PDFDrive )

348 Part IV Disorders of Hematopoietic Cell Development

TABLE Genetic Causes of Human Thrombopoiesis Disorders—cont’d
28.1
Disease Inheritance Mutated Gene Theme Comments Diagnosis
Gray platelet syndrome AD-AR XL NBEAL2, Alpha granule Giant “pale” platelets. Variable Platelet EM; DNA
GFI1b defect bleeding disorder. Mild red sequencing
GATA1 blood cell anisopoikilocytosis in
some cases.
Platelet-type vWD AD GPIba Binds to vWF Platelet count decreases with Ristocetin titration; vWF
to easily stress multimer analysis; vWF
binding studies
Filamin-related XL FLNA Cytoskeletal Platelets small to large size DNA sequencing
thrombocytopenia defect
Tubulin-related AD TUBB1 Cytoskeletal Giant platelets DNA sequencing
thrombocytopenia defect
GATA1-related disease XL GATA1 Transcription Can also have anemia, DNA sequencing
factor β-thalassemia, and/or
dyserythropoiesis
Thrombocytopenia AR ABCG5, Channel-opathy Stomatocytes, possible anemia, DNA sequencing
associated with ABCG8 tendon xanthomas,
sitosterolemia atherosclerosis
Normal-Size Platelets
Thrombocytopenia with AR RBM8A RNA binding Bilateral radial aplasia ± other X-ray; FISH (for
absent radii (TAR) (1q21.1 del) protein malformations. microdeletion)
Thrombocytopenia often resolves
by 12−24 mo.
CAMT AR MPL Cytokine Reduced Mks; can evolve into full DNA sequencing; TPO
receptor BM failure levels
Familial platelet AD RUNX1 ETV6 Transcription Associated platelet dysfunction; DNA sequencing
disorder with factor ~35% risk of developing MDS/
propensity to develop leukemia. Red blood cell
AML (FPD/AML) macrocytosis.
ANKRD26-related AD ANRKD26 Cytoskeletal, Associated platelet dysfunction; DNA sequencing
thrombocytopenia signaling increased risk of leukemia
(THC2) defect?
CTRUS AD HOXA11, Transcription Reduced Mks; cannot pronate X-ray; DNA sequencing
MECOM factor distal arms; risk for BM failure
(EVI1) and leukemia?
CYCS-related AD CYCS Cytochrome c DNA sequencing
thrombocytopenia
Small Platelets
Wiskott-Aldrich XL WASP Cytoskeletal Severe immunodeficiency; eczema; WASP western blot; DNA
syndrome defect platelet dysfunction sequencing
X-linked XL WASP Cytoskeletal No or mild immunodeficiency; WASP western blot; DNA
thrombocytopenia defect platelet dysfunction sequencing
Nonthrombocytopenic
Normal-Size Platelets
Glanzmann AR ITGA2B ITGB3 Integrin Bleeding tendency Platelet aggregation
thrombocythemia deficiency (absent response to all
agonists except
ristocetin); flow
cytometry
Hermansky-Pudlak AR HPS1-8 Granule defect Mild to moderate bleeding Platelet EM; DNA
syndrome tendency. Oculocutaneous sequencing
albinism, rotary nystagmus,
pulmonary fibrosis. Higher
frequency in Puerto Rico
Chediak-Higashi Autosomal LYST Granule defect Bleeding tendency, immune Platelet EM; DNA
syndrome dysfunction, partial albinism; sequencing; flow
can develop lymphoproliferative cytometry?
disorder
AD, Autosomal dominant; AR, autosomal recessive; BM, bone marrow; CAMT, congenital amegakaryocytic thrombocytopenia; CTRUS, congenital thrombocytopenia with
radio-ulnar synostosis; EM, electron microscopy; FISH, fluorescence in situ hybridization; MDS, myelodysplastic syndrome; Mks, megakaryocytes; vWD, von Willebrand
disease, vWF, von Willebrand factor; XL, X-linked.