TY - JOUR
T1 - Thrombocytopenia-absent radius (TAR) syndrome due to compound inheritance for a 1q21.1 microdeletion and a low-frequency noncoding RBM8A SNP
T2 - A new familial case
AU - Tassano, Elisa
AU - Gimelli, Stefania
AU - Divizia, Maria Teresa
AU - Lerone, Margherita
AU - Vaccari, Carlotta
AU - Puliti, Aldamaria
AU - Gimelli, Giorgio
PY - 2015/11/5
Y1 - 2015/11/5
N2 - 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. Discussion: 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. Conclusion: In this study, we discuss other factors that could influence the overall phenotype of patients affected by TAR syndrome.
AB - 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. Discussion: 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. Conclusion: In this study, we discuss other factors that could influence the overall phenotype of patients affected by TAR syndrome.
KW - 1q21.1 microdeletion
KW - Array-CGH
KW - RBM8A SNPs
KW - TAR syndrome
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U2 - 10.1186/s13039-015-0188-6
DO - 10.1186/s13039-015-0188-6
M3 - Article
AN - SCOPUS:84946213902
VL - 8
JO - Molecular Cytogenetics
JF - Molecular Cytogenetics
SN - 1755-8166
IS - 1
M1 - 87
ER -