Molecular diagnosis of thrombocytopenia‐absent radius syndrome using next‐generation sequencing. (20th June 2016)

• Record Type: Journal Article
• Authors: Nicchia, E.; Giordano, P.; Greco, C.; De Rocco, D.; Savoia, A.
• Is Part Of: International journal of laboratory hematology. Volume 38:Number 4(2016:Aug.)
• Page Start: 412
• Page End: 418
• Publication Date: 2016-06-20
• Subjects: Thrombocytopenia‐absent radius (TAR) syndrome -- next‐generation sequencing (NGS) -- ion PGM sequencing -- copy‐number variations (CNVs) -- point mutation; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; Hematology -- Periodicals; 616.15005
• DOI: 10.1111/ijlh.12516
• Languages: English
• ISSNs: 1751-5521

Abstract

Summary: 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.