title: 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.
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 noncoding RBM8A 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 the RBM8A rs139428292 variant in hemizygous state, inherited from the father and the mother, respectively. A second aborted fetus presented TAR features and 1q21.1 microdeletion.
  
  
  CONCLUSIONS
  The complex inheritance pattern resulted in reduced expression of Y14, the protein encoded by RBM8A, 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.
  
  
  CONCLUSIONS
  In this study, we discuss other factors that could influence the overall phenotype of patients affected by TAR syndrome.
authors.affiliation: Laboratorio di Citogentica, Istituto Giannina Gaslini, L.go G.Gaslini 5, 16147 Genoa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Tassano
authors.affiliation: Service of Genetic Medicine, University Hospitals of Geneva, 1211 Geneva, Switzerland.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gimelli
authors.affiliation: U.O.C. Medical Genetics, Istituto Giannina Gaslini, 16147 Genoa, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Divizia
authors.affiliation: U.O.C. Medical Genetics, Istituto Giannina Gaslini, 16147 Genoa, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Lerone
authors.affiliation: DiNOGMI, University of Genoa, 16147 Genoa, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Vaccari
authors.affiliation: U.O.C. Medical Genetics, Istituto Giannina Gaslini, 16147 Genoa, Italy ; DiNOGMI, University of Genoa, 16147 Genoa, Italy.
authors.forename: Aldamaria
authors.initials: A
authors.lastname: Puliti
authors.affiliation: Laboratorio di Citogentica, Istituto Giannina Gaslini, L.go G.Gaslini 5, 16147 Genoa, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gimelli
keywords: 1q21.1 microdeletion; Array-CGH; RBM8A SNPs; TAR syndrome