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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

Results of Sanger sequencing of the rs139428292 variant (G > A) obtained from the patient and his unaffected mother and his unaffected brother
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Fig4: Results of Sanger sequencing of the rs139428292 variant (G > A) obtained from the patient and his unaffected mother and his unaffected brother

Mentions: The family were analysed for the rs139428292 (G > A) and the rs201779890 (G > C) SNPs of RBM8A gene by direct sequencing. The analysis of rs139428292 showed that the patient harboured the minor (A) allele, which was inherited from his healthy mother. The father and the healthy brother were both homozygous for the major (G) allele. All family members carried the major (G) allele of rs201779890 in a homozygous state (Fig. 4).Fig. 4


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)

Results of Sanger sequencing of the rs139428292 variant (G > A) obtained from the patient and his unaffected mother and his unaffected brother
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig4: Results of Sanger sequencing of the rs139428292 variant (G > A) obtained from the patient and his unaffected mother and his unaffected brother
Mentions: The family were analysed for the rs139428292 (G > A) and the rs201779890 (G > C) SNPs of RBM8A gene by direct sequencing. The analysis of rs139428292 showed that the patient harboured the minor (A) allele, which was inherited from his healthy mother. The father and the healthy brother were both homozygous for the major (G) allele. All family members carried the major (G) allele of rs201779890 in a homozygous state (Fig. 4).Fig. 4

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