XLTT
MCID: THR051
MIFTS: 44

Thrombocytopenia with Beta-Thalassemia, X-Linked (XLTT)

Categories: Blood diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Thrombocytopenia with Beta-Thalassemia, X-Linked

MalaCards integrated aliases for Thrombocytopenia with Beta-Thalassemia, X-Linked:

Name: Thrombocytopenia with Beta-Thalassemia, X-Linked 57 72 13 39
Thrombocytopenia, Platelet Dysfunction, Hemolysis, and Imbalanced Globin Synthesis 57 12 29 6 44 70
Xltt 57 12 58 72
Gata1-Related X-Linked Cytopenia 12 25 29
Beta-Thalassemia-X-Linked Thrombocytopenia Syndrome 12 58
X-Linked Thrombocytopenia with Beta-Thalassemia 12 15
Thrombocytopenia Platelet Dysfunction Hemolysis and Imbalanced Globin Synthesis 72

Characteristics:

Orphanet epidemiological data:

58
beta-thalassemia-x-linked thrombocytopenia syndrome
Inheritance: X-linked recessive;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
x-linked recessive

Miscellaneous:
three unrelated families have been reported (last curated june 2012)


HPO:

31
thrombocytopenia with beta-thalassemia, x-linked:
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare haematological diseases


Summaries for Thrombocytopenia with Beta-Thalassemia, X-Linked

UniProtKB/Swiss-Prot : 72 Thrombocytopenia with beta-thalassemia, X-linked: An unusual form of thrombocytopenia associated with beta-thalassemia. Patients have splenomegaly and petechiae, moderate thrombocytopenia, prolonged bleeding time due to platelet dysfunction, reticulocytosis and unbalanced (hemo)globin chain synthesis resembling that of beta- thalassemia minor.

MalaCards based summary : Thrombocytopenia with Beta-Thalassemia, X-Linked, also known as thrombocytopenia, platelet dysfunction, hemolysis, and imbalanced globin synthesis, is related to dyserythropoietic anemia and thrombocytopenia and thalassemia, and has symptoms including petechiae of skin An important gene associated with Thrombocytopenia with Beta-Thalassemia, X-Linked is GATA1 (GATA Binding Protein 1), and among its related pathways/superpathways are Response to elevated platelet cytosolic Ca2+ and Signaling events mediated by HDAC Class I. Affiliated tissues include bone marrow, bone and myeloid, and related phenotypes are splenomegaly and anemia

Disease Ontology : 12 A hematopoietic system disease characterized by variable thrombocytopenia, hemolytic anemia, splenomegaly, and abnormalities in hemoglobin chain synthesis resulting in imbalance between the alpha and beta chains that has material basis in homozygous or hemizygous missense mutation in the DNA binding domain of GATA1 on chromosome Xp11.23.

OMIM® : 57 XLTT is an X-linked recessive hematologic disorder characterized by variable thrombocytopenia, hemolytic anemia, splenomegaly, and abnormalities in hemoglobin chain synthesis (summary by Ciovacco et al., 2008 and Millikan et al., 2011). (314050) (Updated 20-May-2021)

GeneReviews: NBK1364

Related Diseases for Thrombocytopenia with Beta-Thalassemia, X-Linked

Diseases related to Thrombocytopenia with Beta-Thalassemia, X-Linked via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 42)
# Related Disease Score Top Affiliating Genes
1 dyserythropoietic anemia and thrombocytopenia 32.5 ZFPM1 GATA1
2 thalassemia 30.6 HBG1 GATA1
3 thrombocytopenia 29.1 ZFPM1 VPS33B NBEAL2 GP9 GP6 GATA1
4 porphyria, congenital erythropoietic 10.9
5 hydrops fetalis, nonimmune 10.2
6 lymphatic malformation 7 10.2
7 hemosiderosis 10.2
8 neutropenia 10.2
9 porphyria 10.2
10 rare hereditary hemochromatosis 10.2
11 thrombocytopenia 1 10.2 ZFPM1 GATA1
12 fetal hemoglobin quantitative trait locus 1 10.0 HBG2 HBG1
13 pseudo-von willebrand disease 9.9 GP9 GP6 GATA1
14 thalassemia minor 9.9 KLF1 GATA1
15 anemia, congenital dyserythropoietic, type iii 9.9 KLF1 GATA1
16 blood protein disease 9.9 HBG2 HBG1
17 anemia, congenital dyserythropoietic, type ib 9.9 KLF1 GATA1
18 anemia, congenital dyserythropoietic, type iv 9.9 KLF1 GATA1
19 spherocytosis, type 3 9.8 KLF1 GATA1
20 glanzmann thrombasthenia 1 9.8 GP9 GP6
21 anemia, congenital dyserythropoietic, type ia 9.8 KLF1 GATA1
22 cutaneous porphyria 9.8 ZFPM1 KLF1 GATA1
23 hypotrichosis 2 9.8 ZFPM1 KLF1 GATA1
24 spherocytosis, type 4 9.7 KLF1 HBG2 GATA1
25 acute erythroid leukemia 9.7 KLF1 HBG1 GATA1
26 hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome 9.7 KLF1 HBG2 HBG1
27 hemolytic anemia 9.7 KLF1 HBG2 HBG1
28 hermansky-pudlak syndrome 9.6 VPS33B SLC35D3 NBEAL2
29 hemoglobin h disease 9.6 KLF1 HBG2 HBG1
30 hereditary persistence of fetal hemoglobin-sickle cell disease syndrome 9.6 KLF1 HBG2 HBG1
31 congenital dyserythropoietic anemia 9.6 KLF1 GATA1
32 bernard-soulier syndrome 9.6 NBEAL2 GP9 GP6 GATA1
33 blood platelet disease 9.6 NBEAL2 GP9 GP6 GATA1
34 blood coagulation disease 9.6 NBEAL2 GP9 GP6 GATA1
35 beta-thalassemia 9.5 KLF1 HBG2 HBG1 GATA1
36 spherocytosis, type 2 9.5 KLF1 HBG2 HBG1 GATA1
37 congenital hemolytic anemia 9.5 KLF1 HBG2 HBG1 GATA1
38 hemoglobinopathy 9.5 KLF1 HBG2 HBG1 GATA1
39 alpha-thalassemia 9.5 KLF1 HBG2 HBG1 GATA1
40 deficiency anemia 9.4 KLF1 HBG2 HBG1 GATA1
41 hereditary spherocytosis 9.3 ZFPM1 KLF1 HBG2 HBG1 GATA1
42 gray platelet syndrome 9.3 VPS33B NBEAL2 GP9 GP6 GATA1

Graphical network of the top 20 diseases related to Thrombocytopenia with Beta-Thalassemia, X-Linked:



Diseases related to Thrombocytopenia with Beta-Thalassemia, X-Linked

Symptoms & Phenotypes for Thrombocytopenia with Beta-Thalassemia, X-Linked

Human phenotypes related to Thrombocytopenia with Beta-Thalassemia, X-Linked:

58 31 (show all 13)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 splenomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001744
2 anemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001903
3 abnormal hemoglobin 58 31 hallmark (90%) Very frequent (99-80%) HP:0011902
4 thrombocytopenia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001873
5 abnormal platelet function 58 31 hallmark (90%) Very frequent (99-80%) HP:0011869
6 abnormal bleeding 58 31 hallmark (90%) Very frequent (99-80%) HP:0001892
7 hemolytic anemia 31 frequent (33%) HP:0001878
8 hirsutism 31 occasional (7.5%) HP:0001007
9 epistaxis 31 HP:0000421
10 petechiae 31 HP:0000967
11 bruising susceptibility 31 HP:0000978
12 prolonged bleeding time 31 HP:0003010
13 reticulocytosis 31 HP:0001923

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Abdomen Spleen:
splenomegaly

Head And Neck Nose:
epistaxis

Skin Nails Hair Hair:
hirsutism (1 patient)

Hematology:
thrombocytopenia
prolonged bleeding time
reticulocytosis
enlarged platelets
increased alpha/beta globin ratio in reticulocytes
more
Skin Nails Hair Skin:
petechiae
easy bruisability
photosensitivity bullous dermatitis (1 patient)

Laboratory Abnormalities:
decreased uros activity (1 patient)

Clinical features from OMIM®:

314050 (Updated 20-May-2021)

UMLS symptoms related to Thrombocytopenia with Beta-Thalassemia, X-Linked:


petechiae of skin

MGI Mouse Phenotypes related to Thrombocytopenia with Beta-Thalassemia, X-Linked:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.23 GATA1 GP6 GP9 KLF1 NBEAL2 SLC35D3

Drugs & Therapeutics for Thrombocytopenia with Beta-Thalassemia, X-Linked

Search Clinical Trials , NIH Clinical Center for Thrombocytopenia with Beta-Thalassemia, X-Linked

Cochrane evidence based reviews: thrombocytopenia, platelet dysfunction, hemolysis, and imbalanced globin synthesis

Genetic Tests for Thrombocytopenia with Beta-Thalassemia, X-Linked

Genetic tests related to Thrombocytopenia with Beta-Thalassemia, X-Linked:

# Genetic test Affiliating Genes
1 Thrombocytopenia, Platelet Dysfunction, Hemolysis, and Imbalanced Globin Synthesis 29 GATA1
2 Gata1-Related X-Linked Cytopenia 29 GATA1

Anatomical Context for Thrombocytopenia with Beta-Thalassemia, X-Linked

MalaCards organs/tissues related to Thrombocytopenia with Beta-Thalassemia, X-Linked:

40
Bone Marrow, Bone, Myeloid

Publications for Thrombocytopenia with Beta-Thalassemia, X-Linked

Articles related to Thrombocytopenia with Beta-Thalassemia, X-Linked:

(show top 50) (show all 60)
# Title Authors PMID Year
1
X-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation. 25 57 6 61
17209061 2007
2
Congenital erythropoietic porphyria due to a mutation in GATA1: the first trans-acting mutation causative for a human porphyria. 25 6 57
17148589 2007
3
X-linked thrombocytopenia with thalassemia from a mutation in the amino finger of GATA-1 affecting DNA binding rather than FOG-1 interaction. 25 6 57
12200364 2002
4
X-linked syndrome of platelet dysfunction, thrombocytopenia, and imbalanced globin chain synthesis with hemolysis. 25 6 57
871527 1977
5
Why the disorder induced by GATA1 Arg216Gln mutation should be called "X-linked thrombocytopenia with thalassemia" rather than "X-linked gray platelet syndrome". 6 57
17881640 2007
6
Effects of the R216Q mutation of GATA-1 on erythropoiesis and megakaryocytopoiesis. 6 25 61
14691578 2004
7
Mapping of a syndrome of X-linked thrombocytopenia with Thalassemia to band Xp11-12: further evidence of genetic heterogeneity of X-linked thrombocytopenia. 61 6 25
10733494 2000
8
Analysis of disease-causing GATA1 mutations in murine gene complementation systems. 25 6
23704091 2013
9
Congenital erythropoietic porphyria: mutation update and correlations between genotype and phenotype. 6 25
19268002 2009
10
Selective impairment of platelet activation to collagen in the absence of GATA1. 6 25
15701726 2005
11
The porphyrias: recent advances. 25 6
3521939 1986
12
Human phenotypes associated with GATA-1 mutations. 57 61
18930124 2008
13
X-linked thrombocytopenia with thalassemia displays bone marrow reticulin fibrosis and enhanced angiogenesis: comparisons with primary myelofibrosis. 61 25
25421114 2015
14
Inherited thrombocytopenia due to GATA-1 mutations. 57
22102271 2011
15
Paraplegia associated with the use of oxidized cellulose in posterolateral thoracotomy incisions. 6
2200364 1990
16
A Child With Dyserythropoietic Anemia and Megakaryocyte Dysplasia Due to a Novel 5'UTR GATA1s Splice Mutation. 25
26713410 2016
17
Congenital erythropoietic porphyria linked to GATA1-R216W mutation: challenges for diagnosis. 25
25251786 2015
18
Recurrent GATA1 mutations in Diamond-Blackfan anaemia. 25
24766296 2014
19
Loss of GATA-1 full length as a cause of Diamond-Blackfan anemia phenotype. 25
24453067 2014
20
X-linked sideroblastic anemia due to ALAS2 intron 1 enhancer element GATA-binding site mutations. 25
24166784 2014
21
Identification of a novel erythroid-specific enhancer for the ALAS2 gene and its loss-of-function mutation which is associated with congenital sideroblastic anemia. 25
23935018 2014
22
Novel GATA1 mutation in residue D218 leads to macrothrombocytopenia and clinical bleeding problems. 25
23971719 2014
23
GATA1-mutant clones are frequent and often unsuspected in babies with Down syndrome: identification of a population at risk of leukemia. 25
24021668 2013
24
A novel GATA1 mutation (Stop414Arg) in a family with the rare X-linked blood group Lu(a-b-) phenotype and mild macrothrombocytic thrombocytopenia. 25
23278136 2013
25
Naturally occurring oncogenic GATA1 mutants with internal deletions in transient abnormal myelopoiesis in Down syndrome. 25
23440243 2013
26
Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia. 25
22706301 2012
27
Acute megakaryoblastic leukaemia (AMKL) and transient myeloproliferative disorder (TMD) in Down syndrome: a multi-step model of myeloid leukaemogenesis. 25
19594743 2009
28
Congenital transfusion-dependent anemia and thrombocytopenia with myelodysplasia due to a recurrent GATA1(G208R) germline mutation. 25
17713552 2008
29
Platelet pathology in carriers of the X-linked GATA-1 macrothrombocytopenia. 25
18041654 2007
30
Platelet pathology in sex-linked GATA-1 dyserythropoietic macrothrombocytopenia II. Cytochemistry. 25
17763153 2007
31
The gray platelet syndrome: clinical spectrum of the disease. 25
16442192 2007
32
An inherited mutation leading to production of only the short isoform of GATA-1 is associated with impaired erythropoiesis. 25
16783379 2006
33
Transcription factor GATA-1 and Down syndrome leukemogenesis. 25
16840187 2006
34
GATA-1: one protein, many partners. 25
16095949 2006
35
AML patients with Down syndrome have a high cure rate with AML-BFM therapy with reduced dose intensity. 25
15920490 2005
36
Developmental stage-selective effect of somatically mutated leukemogenic transcription factor GATA1. 25
15895080 2005
37
GATA1 in normal and malignant hematopoiesis. 25
15659348 2005
38
GATA1 function, a paradigm for transcription factors in hematopoiesis. 25
15684376 2005
39
GATA1 mutations in Down syndrome: implications for biology and diagnosis of children with transient myeloproliferative disorder and acute megakaryoblastic leukemia. 25
15390312 2005
40
Origins of leukaemia in children with Down syndrome. 25
15630411 2005
41
Dyserythropoietic anemia and thrombocytopenia due to a novel mutation in GATA-1. 25
16103636 2005
42
Inherited thrombocytopenias: molecular mechanisms. 25
15497094 2004
43
Application of a diagnostic algorithm for inherited thrombocytopenias to 46 consecutive patients. 25
15477207 2004
44
Natural history of GATA1 mutations in Down syndrome. 25
14656875 2004
45
Inherited thrombocytopenia: when a low platelet count does not mean ITP. 25
14504084 2004
46
Cooperation between the GATA and RUNX factors Serpent and Lozenge during Drosophila hematopoiesis. 25
14657024 2003
47
A tissue-specific knockout reveals that Gata1 is not essential for Sertoli cell function in the mouse. 25
12954777 2003
48
RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation. 25
12576332 2003
49
Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome. 25
12172547 2002
50
Different substitutions at residue D218 of the X-linked transcription factor GATA1 lead to altered clinical severity of macrothrombocytopenia and anemia and are associated with variable skewed X inactivation. 25
11809723 2002

Variations for Thrombocytopenia with Beta-Thalassemia, X-Linked

ClinVar genetic disease variations for Thrombocytopenia with Beta-Thalassemia, X-Linked:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GATA1 NM_002049.3(GATA1):c.647G>A (p.Arg216Gln) SNV Pathogenic 10428 rs104894809 GRCh37: X:48650778-48650778
GRCh38: X:48792371-48792371
2 GATA1 NM_002049.3(GATA1):c.646C>T (p.Arg216Trp) SNV Pathogenic 31943 rs387907207 GRCh37: X:48650777-48650777
GRCh38: X:48792370-48792370
3 GATA1 NM_002049.3(GATA1):c.94G>A (p.Val32Ile) SNV Uncertain significance 465135 rs782698349 GRCh37: X:48649610-48649610
GRCh38: X:48791203-48791203
4 GATA1 NM_002049.3(GATA1):c.419G>A (p.Arg140Gln) SNV Uncertain significance 533694 rs997764249 GRCh37: X:48650449-48650449
GRCh38: X:48792042-48792042

UniProtKB/Swiss-Prot genetic disease variations for Thrombocytopenia with Beta-Thalassemia, X-Linked:

72
# Symbol AA change Variation ID SNP ID
1 GATA1 p.Arg216Gln VAR_033114 rs104894809

Expression for Thrombocytopenia with Beta-Thalassemia, X-Linked

Search GEO for disease gene expression data for Thrombocytopenia with Beta-Thalassemia, X-Linked.

Pathways for Thrombocytopenia with Beta-Thalassemia, X-Linked

GO Terms for Thrombocytopenia with Beta-Thalassemia, X-Linked

Cellular components related to Thrombocytopenia with Beta-Thalassemia, X-Linked according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transcriptional repressor complex GO:0017053 9.16 ZFPM1 GATA1
2 hemoglobin complex GO:0005833 8.96 HBG2 HBG1
3 haptoglobin-hemoglobin complex GO:0031838 8.62 HBG2 HBG1

Biological processes related to Thrombocytopenia with Beta-Thalassemia, X-Linked according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hemostasis GO:0007599 9.48 GP9 GP6
2 hydrogen peroxide catabolic process GO:0042744 9.46 HBG2 HBG1
3 embryonic hemopoiesis GO:0035162 9.43 ZFPM1 GATA1
4 erythrocyte differentiation GO:0030218 9.43 ZFPM1 KLF1 GATA1
5 oxygen transport GO:0015671 9.4 HBG2 HBG1
6 megakaryocyte differentiation GO:0030219 9.37 ZFPM1 GATA1
7 transcriptional activation by promoter-enhancer looping GO:0071733 9.32 ZFPM1 GATA1
8 regulation of definitive erythrocyte differentiation GO:0010724 9.16 ZFPM1 GATA1
9 platelet formation GO:0030220 9.13 ZFPM1 NBEAL2 GATA1
10 blood coagulation GO:0007596 9.1 ZFPM1 HBG2 HBG1 GP9 GP6 GATA1

Molecular functions related to Thrombocytopenia with Beta-Thalassemia, X-Linked according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II transcription factor binding GO:0001085 9.4 ZFPM1 GATA1
2 peroxidase activity GO:0004601 9.37 HBG2 HBG1
3 oxygen binding GO:0019825 9.32 HBG2 HBG1
4 oxygen carrier activity GO:0005344 9.26 HBG2 HBG1
5 organic acid binding GO:0043177 9.16 HBG2 HBG1
6 haptoglobin binding GO:0031720 8.96 HBG2 HBG1
7 hemoglobin alpha binding GO:0031721 8.62 HBG2 HBG1

Sources for Thrombocytopenia with Beta-Thalassemia, X-Linked

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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