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

E. Nicchia, P. Giordano, C. Greco, D. De Rocco, A. Savoia

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)412-418
Number of pages7
JournalInternational Journal of Laboratory Hematology
Issue number4
Publication statusPublished - Aug 1 2016


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

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical
  • Hematology


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