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 |
|---|---|
| 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 |
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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 journal › Article
}
TY - JOUR
T1 - Molecular diagnosis of thrombocytopenia-absent radius syndrome using next-generation sequencing
AU - Nicchia, E.
AU - Giordano, P.
AU - Greco, C.
AU - De Rocco, D.
AU - Savoia, A.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
KW - copy-number variations (CNVs)
KW - ion PGM sequencing
KW - next-generation sequencing (NGS)
KW - point mutation
KW - Thrombocytopenia-absent radius (TAR) syndrome
UR - http://www.scopus.com/inward/record.url?scp=84978419145&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84978419145&partnerID=8YFLogxK
U2 - 10.1111/ijlh.12516
DO - 10.1111/ijlh.12516
M3 - Article
VL - 38
SP - 412
EP - 418
JO - International Journal of Laboratory Hematology
JF - International Journal of Laboratory Hematology
SN - 1751-5521
IS - 4
ER -