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 journalArticle

6 Citations (Scopus)

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 languageEnglish
Pages (from-to)412-418
Number of pages7
JournalInternational Journal of Laboratory Hematology
Volume38
Issue number4
DOIs
Publication statusPublished - Aug 1 2016

Fingerprint

Genes
Chromosomes
Alleles
Chromosome Deletion
Genetic Testing
Heterozygote
Point Mutation
Fathers
Thrombocytopenia
Molecular Biology
Statistical methods
Substitution reactions
Nucleotides
Mothers
Ions
Costs and Cost Analysis
Testing
Absent radii and thrombocytopenia
Costs

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

Cite this

Molecular diagnosis of thrombocytopenia-absent radius syndrome using next-generation sequencing. / Nicchia, E.; Giordano, P.; Greco, C.; De Rocco, D.; Savoia, A.

In: International Journal of Laboratory Hematology, Vol. 38, No. 4, 01.08.2016, p. 412-418.

Research output: Contribution to journalArticle

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