Department of Pediatric Allergy-Immunology, Kanuni Sultan Suleyman Research and Training Hospital, Istanbul, Turkey.
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
J Clin Immunol. 2018 Apr;38(3):273-277. doi: 10.1007/s10875-018-0487-x. Epub 2018 Mar 21.
Adenosine deaminase 2 (ADA2) have been reported to cause vasculitic diseases and immunodeficiency recently. Patients present with stroke episodes and rashes mimicking polyarteritis nodosa (PAN). We report a patient who has been followed up with severe neutropenia and found an unexpectedly revealed novel mutation in CECR1 affecting ADA2.
We reviewed medical records and clinical history of the patient. No mutations in other known neutropenia genes such as ELA, G6PC3, HAX1, AP3B1, LAMTOR2, VPS13B, VPS45, GFI1, JAGN1, or WAS could be detected. Sanger sequencing was used to confirm the genetic variants in the patient and relatives.
Genetic analysis by exome sequencing revealed a novel mutation in the gene CECR1 (c.G962A; p.G321E) which segregated perfectly in the relatives.
This is the first DADA2 patient presenting with severe neutropenia. We suggest that in patients with unexplained cytopenias combined with immunodeficiency, fevers of unknown origin and high inflammation markers, DADA2 should be considered.
腺苷脱氨酶 2 (ADA2) 最近被报道可引起血管炎和免疫缺陷。患者表现为类似于结节性多动脉炎 (PAN) 的中风发作和皮疹。我们报告了一位患有严重中性粒细胞减少症的患者，发现了一个出乎意料的新突变，影响 ADA2 的 CECR1。
我们回顾了患者的病历和临床病史。在其他已知的中性粒细胞减少症基因，如 ELA、G6PC3、HAX1、AP3B1、LAMTOR2、VPS13B、VPS45、GFI1、JAGN1 或 WAS 中，未发现突变。对患者及其亲属进行了 Sanger 测序以确认遗传变异。
外显子组测序的基因分析显示，CECR1 基因的一个新突变 (c.G962A;p.G321E) 在亲属中完全分离。
这是首例表现为严重中性粒细胞减少症的 DADA2 患者。我们建议，对于伴有不明原因血细胞减少症、免疫缺陷、不明原因发热和高炎症标志物的患者，应考虑 DADA2。
