Thrombocytopenia absent radius

OBJECTIVE: To describe the ultrasonographic, pathologic and molecular findings in a fetus with TAR syndrome, and to illustrate the contribution of chromosomal microarray analysis (CMA) to the etiological investigation of fetal upper limb reduction defects. CASE REPORT: A 35-year-old woman was referred for Genetic Counseling after pregnancy termination for severe upper limb bilateral phocomelia detected in the second trimester. Fetal autopsy showed severe shortening of the arms and forearms...

Rare genetic diseases and syndromes may appear with unique features in some patients. In genetically-solved cases, this situation indicates a phenotypic expansion of the syndrome with additional features (i.e. the disease-associated gene gives rise to unusual clinical presentation). However, this situation can also hide a multilocus pathogenic variation that cannot be solved genetically except by a massive sequencing approach, such as exome sequencing. Here we describe the case of a child with bilateral radial aplasia, transient thrombocytopenia and anemia, cow's milk intolerance, hypospadias, facial dysmorphism, mild hypothyroidism and umbilical and inguinal hernia...

OBJECTIVE: We present the prenatal diagnosis of a class II 1q21.1 microdeletion in monozygotic (MZ) twins with discordant phenotypes. CASE REPORT: A monochorionic diamniotic twin pair presented with discordant ultrasound anomalies; twin A had cardiovascular abnormalities, while twin B did not. No specific complications were noted in the twins during pregnancy. A single nucleotide polymorphism array revealed an identical class II 1q21.1 microdeletion inherited from a phenotypically normal mother and identified the twins as MZ...

No abstract text is available yet for this article.

Thrombocytopenia-absent radii (TAR) syndrome, characterized by neonatal thrombocytopenia and bilateral radial aplasia with thumbs present, is typically caused by the inheritance of a 1q21.1 deletion and a single-nucelotide polymorphism in RBM8A on the nondeleted allele. We evaluated two siblings with TAR-like dysmorphology but lacking thrombocytopenia in infancy. Family NCI-107 participated in an IRB-approved cohort study and underwent comprehensive clinical and genomic evaluations, including aCGH, whole-exome, whole-genome, and targeted sequencing...

Thrombocytopenia absent radius (TAR) syndrome is a rare congenital disorder that is consistently associated with skeletal abnormality and thrombocytopenic haemorrhage. This is a case of a neonate with bilateral absent radius and thrombocytopenia. The rarity of this case prompted this report.

Reduced expression of the Y14 gene is a cause of Thrombocytopenia-absent radius (TAR) syndrome. This gene contains a conserved RNA recognition motif (RRM) in the central region and nuclear localization/export sequences (NLS/NES) in the N-terminal. Y14 and Magoh proteins form tight heterodimers and are the core of exon junction complexes (EJCs), which mediate various processes of mRNA metabolism after transcription. In this report, we found that protein expression levels of exogenously expressed Magoh L136R and Y14 L118R (leucine-to-arginine substitution at amino acid residue 136 and 118 respectively, that results in the formation of the complex being lost) are lower than their wild-types...

BACKGROUND: Rearrangement of the 1q21 region of chromosome 1 manifests as multiple phenotypes, including microcephaly, intellectual disability, dysmorphic facial features, eye abnormalities, cardiac defects, genitourinary anomalies, autism spectrum disorder, psychiatric conditions and seizures. Herein, we describe eight patients with 1q21 deletion and duplication syndromes, and novel deletions and findings. METHODS: Chromosomal microarray analysis was performed to identify the existence of copy number variation...

OBJECTIVE: All of the medical records of fetuses with the sonographic finding of radial ray defects (RRDs) between 2008 and 2015 were retrieved. The associated sonographic findings, cytogenetic results, and necropsy findings were correlated. CASE REPORT: There were 6 cases of RRD. Three cases were bilateral and the other 3 cases were unilateral. The gestational ages at diagnosis were between 12 and 24 weeks gestation. All women carrying fetuses with RRDs opted to terminate the pregnancy...

Thrombocytopenia, defined as a platelet count less than 150 000 per microlitre, occurs in 7%-12% of all pregnancies. Apart from anaemia, it is the most common haematological disorder in pregnancy. Despite its frequent occurrence, thrombocytopenia often leads to difficulties of diagnosis and management in pregnancy. Typically, a pregnant woman will have platelet counts of 150 000 to 450 000 per microlitre and platelet counts may be slightly lower than those of healthy, non-pregnant controls. Approximately, 8% of pregnant women will develop mild thrombocytopenia (100 000-150 000 per microlitre) and while 65% of these women will have no underlying pathology, all pregnant women with platelet counts of less than 100 000 per microlitre should undergo further clinical and laboratory assessment...

Patients with congenital thrombocytopenia have an increased risk of developing myeloid neoplasms. In these cases, the morphologic distinction between disease at baseline and at progression is challenging. This report analyzes clinicopathologic features of congenital thrombocytopenia with long-term follow-up at one referral center. Records from the last 20 years were searched for cases of congenital thrombocytopenia with bone marrow biopsies and peripheral blood smears. The clinical, morphologic, immunophenotypic, and molecular features were analyzed...

The genetic basis of thrombocytopenia-absent radius (TAR) syndrome was recently identified to be related to the RBM8A gene. The encoded protein (known as the Y14 protein) is widely expressed in human cells (including osteoblasts) and plays several essential intracellular functions. Hence, the pathogenesis of radial ray deficiency in thrombocytopeniaabsent radius syndrome remains a mystery. The current paper reviews the pathogenesis of the clinical features of thrombocytopenia-absent radius syndrome and offers a hypothesis of pathogenesis through attenuation of the Fibroblast Growth Factor 8 signal in the mesoderm because of an increased degradation of the Fibroblast Growth Factor Receptor 1...

INTRODUCTION: Thrombocytopenia-absent radius (TAR) syndrome is a rare autosomal recessive disease. Patients are compound heterozygotes for a loss-of-function allele, which in most cases is a large genomic deletion on chromosome 1q21.1 containing the RBM8A gene, and a noncoding variant located in the 5'UTR (rs139428292) or intronic (rs201779890) regions of RBM8A. As the molecular genetic testing in TAR requires multiple techniques for detection of copy-number variations (CNV) and nucleotide substitutions, we tested whether a next-generation sequencing (NGS) approach could identify both alterations...

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Radial deficiencies (RDs), defined as under/abnormal development or absence of any of the structures of the forearm, radial carpal bones and thumb, occur with a live birth incidence ranging from 1 out of 30,000 to 1 out 6,000 newborns and represent about one third/one fourth of all the congenital upper limb anomalies. About half of radial disorders have a mendelian cause and pattern of inheritance, whereas the remaining half appears sporadic with no known gene involved. In sporadic forms certain anomalies, such as thumb or radial hypoplasia, may occur either alone or in association with systemic conditions, like vertebral abnormalities or renal defects...

Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is an inherited bone marrow failure syndrome, characterized by thrombocytopenia and congenital fusion of the radius and ulna. A heterozygous HOXA11 mutation has been identified in two unrelated families as a cause of RUSAT. However, HOXA11 mutations are absent in a number of individuals with RUSAT, which suggests that other genetic loci contribute to RUSAT. In the current study, we performed whole exome sequencing in an individual with RUSAT and her healthy parents and identified a de novo missense mutation in MECOM, encoding EVI1, in the individual with RUSAT...

No abstract text is available yet for this article.

Neonates are predisposed to developing thrombocytopenia and neonates are affected by megakaryocytic disorders such as thrombocytopenia with absent radius syndrome and transient myeloproliferative disorder. Small double stranded non-coding microRNAs (miRNAs) have been shown to crucially involve in the regulation of stem-cell differentiation in normal as well as malignant haematopoiesis. The regulatory mechanism in developmental megakaryocytopoiesis and role of miRNAs in biological differences between adult and neonatal megakaryopoiesis is unknown...

Thrombocytopenia - absent radii (TAR) syndrome is an autosomal recessive genetic rare disorder with hypomegakaryocytic thrombocytopenia and bilateral absent radius that may have additional anomalies. This disorder is characterized by thrombocytopenia resulting in potentially severe bleeding episodes primarily during infancy. We report the case of a 7-day-old term appropriate for gestational age (AGA) male baby, product of non consanguineous marriage presented with bloody loose stool, right sided upper limb deformity and paleness of the body, was diagnosed as TAR syndrome with some atypical presentation...

Thrombocytopenia absent radius (TAR) syndrome is a very rare and infrequently seen congenital disorder with an approximate frequency of 0.42/100,000 live births. It is associated with bilateral absence of radii, hypo-megakaryocytic thrombocytopenia, and presence of both thumbs. The other systems which are affected by TAR syndrome include skeletal, hematologic, and cardiac systems. Intracranial hemorrhages due to thrombocytopenia and cardiac disorders are a common association usually seen with this syndrome and are usual cause of death...