Genes associated with IPDs
Inherited condition . | Gene (location) . | Inheritance . | Key features . |
---|---|---|---|
Microthrombocytic | |||
Wiskott-Aldrich syndrome | WAS (Xp11) | X-linked | Thrombocytopenia, eczema, severe immunodeficiency, small platelets |
X-linked thrombocytopenia | WAS (Xp11-exon2) | X-linked | Small platelets, thrombocytopenia, mild immunodeficiency |
FYB-related thrombocytopenia | FYB (5p13.1) | AR | Small platelets and mild to moderate bleeding |
ARCP1B-related thrombocytopenia | ARCP1B(7q22.1) | AR | Microthrombocytopenia, eosinophilia, inflammatory disease |
Normothrombocytic | |||
Congenital amegakaryocytic thrombocytopenia | MPL (1p34) | AR | Hypomegakaryocytic thrombocytopenia with eventual development of bone marrow failure |
Thrombocytopenia with absent radii | RBM8A (1q21.1) | AR | Thrombocytopenia that improves with age, limb anomalies (normal thumbs) |
Radio-ulnar synostosis with amegakaryocytic thrombocytopenia | HOXA11 (7p15), MECOM (3q26.2) | AD | Severe thrombocytopenia that improves with age, skeletal abnormalities (radio-ulnar synostosis, clinodactyly, syndactyly, hip dysplasia), hearing loss |
Familial platelet disorder with predisposition to AML | RUNX1 (21q22) | AD | Thrombocytopenia, myelodysplasia or AML, platelet dysfunction |
Paris-Trousseau/Jacobsen syndrome | FLI1 (11p24.3) | AR | Thrombocytopenia with large granules and, depending on size of deletion, other symptoms arising from deletion of other genes |
Familial thrombocytopenia 2 | ANKRD26 (10p12.1) | AD | Mild to moderate thrombocytopenia with mild bleeding symptoms, cancer predisposition with risk of myeloid malignancy and MDS |
ETV6-related thrombocytopenia | ETV6 (12p13.2) | AD | Mild to moderate thrombocytopenia, increased risk of hematologic malignancy, including ALL, AML, and MDS |
Monoallelic THPO mutation | THPO (3q27.1) | AD | Minimal to no bleeding with low platelet count |
CYCS-related thrombocytopenia | CYCS (7p15) | AD | Thrombocytopenia without significant bleeding due to abnormal platelet release |
Macrothrombocytic | |||
Bernard-Soulier syndrome | GPIBA (17p13), GPIBB (22q11), GPIX (3q21) | AR, AD | Platelet dysfunction with large platelets |
Velocardiofacial syndrome | 22q11 | AD | Cardiac anomalies, cleft palate, hypocalcemia, thymic aplasia, and typical facies. BSS-like thrombocytopenia with or without autoimmune etiology |
Platelet-type von Willebrand disease | GPIBA (17p13) | AD | Decreased high molecular weight VWF multimers with thrombocytopenia (increased platelet affinity for VWF) |
MYH9-related disease | MYH9 (22q11.2) | AD | Large platelets, leukocyte inclusions; may have sensorineural hearing loss, cataracts, glomerulonephritis, or renal failure |
Gray platelet syndrome | NBEAL2 (3p21) | AD, AR | Large, pale platelets with absence of α granules |
GATA-1 mutation of X-linked thrombocytopenia with thalassemia | GATA1 (Xp11.23) | X-linked | Thrombocytopenia with variable anemia |
SLFN14-related thrombocytopenia | SLFN14 (17q12) | AD | Variable platelet size with mild to severe bleeding and impaired platelet function |
Stormorken syndrome/York platelet syndrome | STIM1 (11p15) or ORAI1 (12q24.31) | AD | Tubular aggregate myopathy and platelet disorder with decreased α granules, thrombocytopenia, abnormal function, and mild to moderate bleeding |
TUBB1-related thrombocytopenia | TUBB1 (20q13.32) | AD | Spherocytic platelets and decreased cardiovascular disease in males |
Macrothrombocytopenia with filamin A mutations | FLNA (Xq28) | X-Linked | Abnormal granule distribution on EM, mild to moderate thrombocytopenia, impaired aggregation to collagen |
GFI1b-related thrombocytopenia | GFI1b (9q24) | AD | Moderate to severe bleeding with gray platelet-like phenotype with absent α granules and variable red cell anisocytosis |
TRPM7-related thrombocytopenia | TRPM7 (15q21.2) | AD | Large platelets with aberrant granule distribution and mild bleeding |
ACTN1-related thrombocytopenia | ACTN1 (14q24) | AD | Large platelets with absent to mild bleeding |
PRKACG-related thrombocytopenia | PRKACG (9q21) | AR | Large platelets with aberrant FLNA expression and impaired function |
TPM4-related thrombocytopenia | TPM4 (19p13.1) | AD | Large platelets with mild bleeding |
DIAPH1-related thrombocytopenia | DIAPH1 (5q31.3) | AD | Sensorineural hearing loss, large platelets |
SRC-related thrombocytopenia | SRC (20q11.23) | AD | Moderate to severe bleeding with hypogranular platelets and impaired platelet function and juvenile onset myelofibrosis, osteoporosis |
ITGA2B/ITGB3-related thrombocytopenia | ITGA2B (17q21) or ITGB3 (17q21) | AD | Moderate bleeding, large platelets, and abnormal function with gain-of-function variants |
Inherited condition . | Gene (location) . | Inheritance . | Key features . |
---|---|---|---|
Microthrombocytic | |||
Wiskott-Aldrich syndrome | WAS (Xp11) | X-linked | Thrombocytopenia, eczema, severe immunodeficiency, small platelets |
X-linked thrombocytopenia | WAS (Xp11-exon2) | X-linked | Small platelets, thrombocytopenia, mild immunodeficiency |
FYB-related thrombocytopenia | FYB (5p13.1) | AR | Small platelets and mild to moderate bleeding |
ARCP1B-related thrombocytopenia | ARCP1B(7q22.1) | AR | Microthrombocytopenia, eosinophilia, inflammatory disease |
Normothrombocytic | |||
Congenital amegakaryocytic thrombocytopenia | MPL (1p34) | AR | Hypomegakaryocytic thrombocytopenia with eventual development of bone marrow failure |
Thrombocytopenia with absent radii | RBM8A (1q21.1) | AR | Thrombocytopenia that improves with age, limb anomalies (normal thumbs) |
Radio-ulnar synostosis with amegakaryocytic thrombocytopenia | HOXA11 (7p15), MECOM (3q26.2) | AD | Severe thrombocytopenia that improves with age, skeletal abnormalities (radio-ulnar synostosis, clinodactyly, syndactyly, hip dysplasia), hearing loss |
Familial platelet disorder with predisposition to AML | RUNX1 (21q22) | AD | Thrombocytopenia, myelodysplasia or AML, platelet dysfunction |
Paris-Trousseau/Jacobsen syndrome | FLI1 (11p24.3) | AR | Thrombocytopenia with large granules and, depending on size of deletion, other symptoms arising from deletion of other genes |
Familial thrombocytopenia 2 | ANKRD26 (10p12.1) | AD | Mild to moderate thrombocytopenia with mild bleeding symptoms, cancer predisposition with risk of myeloid malignancy and MDS |
ETV6-related thrombocytopenia | ETV6 (12p13.2) | AD | Mild to moderate thrombocytopenia, increased risk of hematologic malignancy, including ALL, AML, and MDS |
Monoallelic THPO mutation | THPO (3q27.1) | AD | Minimal to no bleeding with low platelet count |
CYCS-related thrombocytopenia | CYCS (7p15) | AD | Thrombocytopenia without significant bleeding due to abnormal platelet release |
Macrothrombocytic | |||
Bernard-Soulier syndrome | GPIBA (17p13), GPIBB (22q11), GPIX (3q21) | AR, AD | Platelet dysfunction with large platelets |
Velocardiofacial syndrome | 22q11 | AD | Cardiac anomalies, cleft palate, hypocalcemia, thymic aplasia, and typical facies. BSS-like thrombocytopenia with or without autoimmune etiology |
Platelet-type von Willebrand disease | GPIBA (17p13) | AD | Decreased high molecular weight VWF multimers with thrombocytopenia (increased platelet affinity for VWF) |
MYH9-related disease | MYH9 (22q11.2) | AD | Large platelets, leukocyte inclusions; may have sensorineural hearing loss, cataracts, glomerulonephritis, or renal failure |
Gray platelet syndrome | NBEAL2 (3p21) | AD, AR | Large, pale platelets with absence of α granules |
GATA-1 mutation of X-linked thrombocytopenia with thalassemia | GATA1 (Xp11.23) | X-linked | Thrombocytopenia with variable anemia |
SLFN14-related thrombocytopenia | SLFN14 (17q12) | AD | Variable platelet size with mild to severe bleeding and impaired platelet function |
Stormorken syndrome/York platelet syndrome | STIM1 (11p15) or ORAI1 (12q24.31) | AD | Tubular aggregate myopathy and platelet disorder with decreased α granules, thrombocytopenia, abnormal function, and mild to moderate bleeding |
TUBB1-related thrombocytopenia | TUBB1 (20q13.32) | AD | Spherocytic platelets and decreased cardiovascular disease in males |
Macrothrombocytopenia with filamin A mutations | FLNA (Xq28) | X-Linked | Abnormal granule distribution on EM, mild to moderate thrombocytopenia, impaired aggregation to collagen |
GFI1b-related thrombocytopenia | GFI1b (9q24) | AD | Moderate to severe bleeding with gray platelet-like phenotype with absent α granules and variable red cell anisocytosis |
TRPM7-related thrombocytopenia | TRPM7 (15q21.2) | AD | Large platelets with aberrant granule distribution and mild bleeding |
ACTN1-related thrombocytopenia | ACTN1 (14q24) | AD | Large platelets with absent to mild bleeding |
PRKACG-related thrombocytopenia | PRKACG (9q21) | AR | Large platelets with aberrant FLNA expression and impaired function |
TPM4-related thrombocytopenia | TPM4 (19p13.1) | AD | Large platelets with mild bleeding |
DIAPH1-related thrombocytopenia | DIAPH1 (5q31.3) | AD | Sensorineural hearing loss, large platelets |
SRC-related thrombocytopenia | SRC (20q11.23) | AD | Moderate to severe bleeding with hypogranular platelets and impaired platelet function and juvenile onset myelofibrosis, osteoporosis |
ITGA2B/ITGB3-related thrombocytopenia | ITGA2B (17q21) or ITGB3 (17q21) | AD | Moderate bleeding, large platelets, and abnormal function with gain-of-function variants |
Reprinted from Lambert31 with permission.
AD, autosomal dominant; ALL, acute lymphocytic leukemia; AML, acute myeloid leukemia; AR, autosomal recessive; BSS, Bernard-Soulier syndrome; EM, electron microscopy; MDS, myelodysplastic syndrome; VWF, von Willebrand factor.