Whole-genome sequencing suggests a role of MIF in the pathophysiology of TEMPI syndrome

•WGS analysis shows complex structural variants of chromosome 2, and duplication of 22q11.23 in one patient with TEMPI syndrome.•Duplication of 22q11.23 in plasma cells may result in elevated level of MIF, which may contribute to the pathophysiology of TEMPI syndrome. TEMPI syndrome (telangiectasias...

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Published in:Blood advances 2021-06, Vol.5 (12), p.2563-2568
Main Authors: Sun, Chunyan, Xu, Jian, Zhang, Bo, Huang, Haifan, Chen, Lei, Yan, Han, Xu, Aoshuang, Zhao, Fei, Huang, Daijuan, Liu, Liqiong, Li, Jian, Hu, Yu
Format: Article
Language:English
Subjects:
Humans
Intramolecular Oxidoreductases
Macrophage Migration-Inhibitory Factors - genetics
Monoclonal Gammopathy of Undetermined Significance
Paraproteinemias
Polycythemia
Stimulus Report
Telangiectasis
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Summary:•WGS analysis shows complex structural variants of chromosome 2, and duplication of 22q11.23 in one patient with TEMPI syndrome.•Duplication of 22q11.23 in plasma cells may result in elevated level of MIF, which may contribute to the pathophysiology of TEMPI syndrome. TEMPI syndrome (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) is a newly defined multisystemic disease with its pathophysiology largely unknown. Here, we report the whole-genome sequencing (WGS) analysis on the tumor-normal paired cells from a patient with TEMPI syndrome. WGS revealed somatic nonsynonymous single-nucleotide variants, including SLC7A8, NRP2, and AQP7. Complex structural variants of chromosome 2 were found, particularly within regions where some putative oncogenes reside. Of potential clinical relevance, duplication of 22q11.23 was identified, and the expression of the located gene macrophage migration inhibitory factor (MIF) was significantly upregulated in 3 patients with TEMPI syndrome. Importantly, the level of serum MIF in one patient with TEMPI syndrome was significantly decreased in accordance with the downtrend of plasma cells, M-protein, hemoglobin, and erythropoietin and the improvement of telangiectasias, perinephric fluid collections, and intrapulmonary shunting after treatment with plasma cell–directed therapy. In conclusion, our study provides insights into the genomic landscape and suggests a role of MIF in the pathophysiology of TEMPI syndrome.
ISSN:2473-9529
2473-9537
DOI:10.1182/bloodadvances.2020003783