Thrombocytopenia-absent radius (TAR) syndrome due to compound inheritance for a 1q21.1 microdeletion and a low-frequency noncoding RBM8A SNP: a new familial case. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Tassano, Elisa; Gimelli, Stefania; Divizia, Maria; Lerone, Margherita; Vaccari, Carlotta; Puliti, Aldamaria; Gimelli, Giorgio
• Is Part Of: Molecular cytogenetics. Volume 8:Issue 1(2015)
• Page Start: 1
• Page End: 7
• Publication Date: 2015-12
• Subjects: 1q21.1 microdeletion -- TAR syndrome -- Array-CGH -- RBM8A SNPs; Cytogenetics -- Periodicals; Chromosomes -- Periodicals; Molecular genetics -- Periodicals; 572.805
• DOI: 10.1186/s13039-015-0188-6
• Languages: English
• ISSNs: 1755-8166

Abstract

Abstract Background Thrombocytopenia-absent radius syndrome (TAR; MIM 274000) is a rare autosomal recessive disorder combining specific skeletal abnormalities with a reduced platelet count. TAR syndrome has been associated with the compound inheritance of an interstitial microdeletion in 1q21.1 and a low frequency noncodingRBM8A SNP. Results Here, we report on a patient with scapulo-humeral hypoplasia, bilateral radio-ulnar agenesis with intact thumbs, bilateral proximal positioning of the first metacarpal, bilateral fifth finger clinodactyly, bilateral radial deviation of the hands, and thrombocytopenia. Molecular studies showed compound heterozygosity for the 1q21.1 microdeletion and theRBM8A rs139428292 variant in hemizygous state, inherited from the father and the mother, respectively. A second aborted fetus presented TAR features and 1q21.1 microdeletion. Discussion The complex inheritance pattern resulted in reduced expression of Y14, the protein encoded byRBM8A, and a component of the core exon-junction complex (EJC) in platelets. Further studies are needed to explain how Y14 insufficiency and subsequent defects of the EJC could cause the skeletal, haematological and additional features of TAR syndrome. In this study, we discuss other factors that could influence the overall phenotype of patients affected by TAR syndrome. Conclusion In this study, we discuss other factors that could influence the overall phenotype of patients affected by TAR syndrome.