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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.

Tassano E, Gimelli S, Divizia MT, Lerone M, Vaccari C, Puliti A, Gimelli G - Mol Cytogenet (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio di Citogentica, Istituto Giannina Gaslini, L.go G.Gaslini 5, 16147 Genoa, Italy.

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.

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.

No MeSH data available.


Related in: MedlinePlus

a The proband (II-2); bilateral absence of radius with thumb conservation and bilateral genu varum. b The fetus (II-3); bilateral radial aplasia
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Fig2: a The proband (II-2); bilateral absence of radius with thumb conservation and bilateral genu varum. b The fetus (II-3); bilateral radial aplasia

Mentions: The child (II-2) (Fig. 2a) is the first male child of apparently healthy nonconsanguineous parents. The mother and the father were 33 and 45 years old respectively at the time of his birth. Fetal movements were poor. Routine ultrasound examination was normal until 23 weeks of gestation when bilateral radial agenesis was demonstrated. The child was born post-term at 43 weeks of gestation by normal vaginal delivery. Birth weight was 2810 g (10th-25th centile). He was admitted to our institute at 4 months of age. Physical examination showed good nutritional status, forehead and right cheek telangiectasia, scapulo-humeral hypoplasia, bilateral radio-ulnar agenesis with intact thumbs, bilateral proximal positioning of the first metacarpal, bilateral fifth finger clinodactyly and bilateral radial deviation of the hands. X-ray confirmed all these skeletal findings. The child also presented thrombocytopenia (40.000/mmc), PTT (43.7 s). The phenotypic features were characteristic of TAR syndrome (MIM 274000).Fig. 2


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.

Tassano E, Gimelli S, Divizia MT, Lerone M, Vaccari C, Puliti A, Gimelli G - Mol Cytogenet (2015)

a The proband (II-2); bilateral absence of radius with thumb conservation and bilateral genu varum. b The fetus (II-3); bilateral radial aplasia
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4635577&req=5

Fig2: a The proband (II-2); bilateral absence of radius with thumb conservation and bilateral genu varum. b The fetus (II-3); bilateral radial aplasia
Mentions: The child (II-2) (Fig. 2a) is the first male child of apparently healthy nonconsanguineous parents. The mother and the father were 33 and 45 years old respectively at the time of his birth. Fetal movements were poor. Routine ultrasound examination was normal until 23 weeks of gestation when bilateral radial agenesis was demonstrated. The child was born post-term at 43 weeks of gestation by normal vaginal delivery. Birth weight was 2810 g (10th-25th centile). He was admitted to our institute at 4 months of age. Physical examination showed good nutritional status, forehead and right cheek telangiectasia, scapulo-humeral hypoplasia, bilateral radio-ulnar agenesis with intact thumbs, bilateral proximal positioning of the first metacarpal, bilateral fifth finger clinodactyly and bilateral radial deviation of the hands. X-ray confirmed all these skeletal findings. The child also presented thrombocytopenia (40.000/mmc), PTT (43.7 s). The phenotypic features were characteristic of TAR syndrome (MIM 274000).Fig. 2

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio di Citogentica, Istituto Giannina Gaslini, L.go G.Gaslini 5, 16147 Genoa, Italy.

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.

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.

No MeSH data available.


Related in: MedlinePlus