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Thrombocytopenia-Absent Radius
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Molecularly, TAR syndrome is linked to a 200-kb interstitial microdeletion of chromosome 1q21.1 resulting in one null RBM8A allele, or polymorphisms in either the 5′-untranslated region or first intron of a hypomorphic RBM8A allele. As the RBM8A gene encodes an RNA-binding protein (Y14), which is a key component of the exon-junction complex (EJC) involved in nuclear export of transcripts, nonsense mediated decay, and translational enhancement, its deletion or alteration abrogates or reduces expression of the hypomorphic allele in a cell type- and developmental stage-specific manner, leading to defective mRNA processing and export [1].
Case 27
Published in Atul B. Mehta, Keith Gomez, Clinical Haematology, 2017
Important causes of neonatal thrombocytopenia are genetic, congenital and acquired. Genetic causes are rare, but include thrombocytopenia with absent radii (TAR) syndrome. Congenital infection (rubella, cytomegalovirus [CMV] and toxoplasmosis) should be excluded by serological tests on mother and culture studies of the neonate. Congenital immune thrombocytopenia may arise through transplacental passage of IgG anti-platelet antibodies in mothers with idiopathic thrombocytopenic purpura, or may present as neonatal alloimmune thrombocytopenia. Mothers who lack certain platelet antigens (most commonly human platelet antigen [HPA]-1a) will make antibodies if sensitised by previous pregnancy or transfusion. Acquired causes include sepsis, disseminated intravascular coagulation and drugs.
Individual conditions grouped according to the international nosology and classification of genetic skeletal disorders*
Published in Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow, Fetal and Perinatal Skeletal Dysplasias, 2012
Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow
Differential diagnosis: severe and similar upper limb anomalies may be present in Fanconi anaemia (p. 460) and Roberts syndrome (p. 467). TAR syndrome is probably the most similar disorder, as it is characterised by radial ray defects and thrombocytopenia, but it does not have a meningoencephalocoele. VATER association (p. 590); Baller-Gerold syndrome in addition has growth retardation, coronal craniosynostosis and poikiloderma.
Changes in megakaryopoiesis over ontogeny and their implications in health and disease
Published in Platelets, 2020
Patricia Davenport, Zhi-Jian Liu, Martha Sola-Visner
TAR syndrome is a rare disorder involving thrombocytopenia and bilateral absence of the radius. Patients present in infancy with thrombocytopenia that often improves with age. Patients with TAR have decreased numbers of MK progenitors in the BM and exhibit defective TPO signaling in their platelets. These defects in TPO signaling result from decreased JAK2 phosphorylation. Interestingly, this defect corrected with age, with adult samples having normal JAK2 phosphorylation in response to TPO signaling, suggesting a developmentally driven pathophysiology that has not yet been elucidated [80]. In regard to the genetic cause of TAR, early studies found a proximal microdeletion of 1.q21.1 that is present in all affected individuals, but the finding of multiple different patterns of inheritance suggested that the 1.q21.1 deletion is required but not sufficient to explain TAR [81]. Subsequent studies elucidated that TAR is caused by the compound inheritance of a rare null allele and one of two low-frequency SNPs in the regulatory regions of RBM8A, which encodes the Y14 subunit of the exon-junction complex. Of the 53 cases with this inheritance pattern, 51 carried a submicroscopic deletion of 1q21.1 that had previously been associated with TAR. As expected, subjects with TAR had reduced Y14 expression in their platelets. However, the mechanisms behind the developmental-stage specific manifestations of TAR syndrome are still not understood [82].
Diagnosis of platelet function disorders: A standardized, rational, and modular flow cytometric approach
Published in Platelets, 2018
Oliver Andres, Katja Henning, Gabriele Strauß, Annerose Pflug, Georgi Manukjan, Harald Schulze
We were curious whether this method may identify altered platelet receptor expression patterns or reactivity in diseases with suspected functional defect. In a large cohort of patients with TAR syndrome, the authors provided evidence that levels of CD42a/b and CD29 were slightly lowered and those of CD49e were markedly reduced in TAR syndrome while lysosomal granule release in response to TRAP6 was also diminished [12]. Interestingly, we could not confirm an elevated expression of the degranulation markers CD62P and CD63 and increased binding of PAC-1 antibody to resting platelets in some patients with sickle cell disease (Supplementary Figure 4), an observation that had been associated with the higher risk of patients to develop thrombotic events [34].