Copy-number variations in adult patients with chronic immune thrombocytopenia

ABSTRACT

Objectives

Immune thrombocytopenia (ITP) is an autoimmune disease with heterogeneous background. FCGR2C mutations were defined in one third of the patients but genetic players have not been fully elucidated yet. Although childhood ITP present as benign, ITP in adulthood is chronic disease with treatment challenges. This study aimed to focus on adult ITP patients using a whole genome genotyping that is valuable approach to identify the responsible genomic regions for the disease.

Methods

Herein 24 adult primary-refractory for ITP patients were evaluated using HumanCytoSNP12BeadChip,Illumina. Forty-six age and sex matched healthy individuals, and ptients awith nonhematological conditions were analyzed as controls. Identified CNV regions were verified by qRTPCR. T-cell receptor beta and delta (TCRB/TCRG) clonality were assessed by heteroduplex analysis in mosaic cases.

Results

Several CNV losses and gains were defined (losses:2q,7q,17q,19p, and gains: 1q,2p,3q,4q,7q,10q,12p,13q,14q,15q,17p,20q,21p,22q,Xp). Mosaic changes of different sizes (0.2-17.77Mb) were identified in five patients and three of them showed clonality. CNV regions that were unique to ITP patients were identified for the first time and among these genes, those related to immune regulation, and cellular trafficking were noteworthy. Conclusion: Identified CNV regions harbor several candidate genes, the functions of which might shed light on the pathogenesis of chronic ITP.

KEYWORDS:

• Immune thrombocytopenia
• copy-number variation
• single nucleotide polymorphism
• whole-genome genotyping
• clonality

Author contributions

Conception – M. Cem Ar, Muge Sayitoglu, Emrah Yucesan; Design – Emrah Yucesan, Ozden Hatirnaz Ng, Muge Sayitoglu; Supervision – Ugur Ozbek, Teoman Soysal, Zafer Baslar, Seniz Ongoren; Fundings – M. Cem Ar, Muge Sayitoglu, Uguz Ozbek; Materials – Emrah Yucesan, Fevzi Firat Yalniz, Hulya Yilmaz, Ayse Salihoglu, Tugce Sudutan; Data Collection and/or Processing – Emrah Yucesan, Ozden Hatirnaz Ng, Fevzi Firat Yalniz, Hulya Yilmaz, Ayse Salihoglu, Ahmet Emre Eskazan, Tugce Sudutan; Analysis and/or Interpretation – Emrah Yucesan, Ozden Hatinaz Ng, Muge Sayitoglu; Literature Review – Ugur Ozbek, Teoman Soysal, Zafer Baslar, Seniz Ongoren, Ahmet Emre Eskazan; Writer – Emrah Yucesan, Ozden Hatirnaz Ng, Muge Sayitoglu, M. Cem Ar.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Acknowledgments

The authors highly appreciate the efforts of Monica Ann Ozkan, MSN, RN, and CPAN in English editing this article.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This paper was funded by the Istanbul University Scientific Research Fund (Grant number: 11021)