Molecular diagnosis of thrombocytopenia-absent radius syndrome using next-generation sequencing

Int J Lab Hematol. 2016 Aug;38(4):412-8. doi: 10.1111/ijlh.12516. Epub 2016 Jun 20.


Introduction: Thrombocytopenia-absent radius (TAR) syndrome is a rare autosomal recessive disease. Patients are compound heterozygotes for a loss-of-function allele, which in most cases is a large genomic deletion on chromosome 1q21.1 containing the RBM8A gene, and a noncoding variant located in the 5'UTR (rs139428292) or intronic (rs201779890) regions of RBM8A. As the molecular genetic testing in TAR requires multiple techniques for detection of copy-number variations (CNV) and nucleotide substitutions, we tested whether a next-generation sequencing (NGS) approach could identify both alterations.

Methods: Two unrelated families were analyzed with Ion PGM sequencing using a target panel of genes responsible for different forms of inherited thrombocytopenia. A statistical quantitative evaluation of amplicon coverage was performed to detect CNV, in particular those on the RBM8A gene.

Results: All the probands were apparently homozygous for the rare allele inherited by the father at the rs139428292 locus, suggesting the presence of a deletion on the maternal chromosome. The statistical analysis confirmed the hemizygous condition of RBM8A.

Conclusion: We concluded that NGS approaches could be used as a cost-effective method for molecular investigation of TAR as they could simultaneously detect CNV and point mutations.

Keywords: Thrombocytopenia-absent radius (TAR) syndrome; copy-number variations (CNVs); ion PGM sequencing; next-generation sequencing (NGS); point mutation.

MeSH terms

  • Adult
  • Chromosome Deletion
  • Congenital Bone Marrow Failure Syndromes
  • DNA Copy Number Variations / genetics
  • Family
  • Female
  • Humans
  • Male
  • Molecular Diagnostic Techniques / methods
  • Molecular Diagnostic Techniques / standards*
  • RNA-Binding Proteins / genetics*
  • Radius
  • Sequence Analysis, DNA / methods
  • Sequence Analysis, DNA / standards
  • Thrombocytopenia / diagnosis*
  • Thrombocytopenia / genetics
  • Upper Extremity Deformities, Congenital / diagnosis*
  • Upper Extremity Deformities, Congenital / genetics


  • RBM8A protein, human
  • RNA-Binding Proteins

Supplementary concepts

  • Absent radii and thrombocytopenia