Abstract
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 language | English |
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Pages (from-to) | 412-418 |
Number of pages | 7 |
Journal | International Journal of Laboratory Hematology |
Volume | 38 |
Issue number | 4 |
DOIs | |
Publication status | Published - Aug 1 2016 |
Keywords
- 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