Novel Mutation in CECR1 Leads to Deficiency of ADA2 with Associated Neutropenia
Novel Mutation in CECR1 Leads to Deficiency of ADA2 with Associated Neutropenia
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DOI：
10.1007/s10875-018-0487-x
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发表时间：
2018-04-01
影响因子：
9.1
通讯作者：
Boztug, Kaan
中科院分区：
文献类型：
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作者：
Cipe, Funda Erol;Aydogmus, Cigdem;Boztug, Kaan
腺苷脱氨酶2（Adenosine Deaminase 2，ADA 2）是近年来发现的引起血管炎和免疫缺陷的重要因子。患者出现类似结节性多动脉炎（PAN）的卒中发作和皮疹。我们报告一位因严重中性粒细胞减少症而接受追踪的病人，意外地发现一个影响ADA 2的CECR 1新突变。未检测到其他已知中性粒细胞减少症基因（如ELA、G6 PC 3、HAX 1、AP 3B 1、LAMTOR 2、VPS 13 B、VPS 45、GFI 1、JAGN 1或WAS）的突变。桑格测序证实了患者及其亲属的遗传变异。通过外显子组测序进行的遗传分析显示，CECR 1基因（c.G962A; p.G321E）中存在一种新的突变，该突变在亲属中完全分离。这是第一例出现严重中性粒细胞减少症的DADA 2患者。我们建议在不明原因血细胞减少症合并免疫缺陷、不明原因发热和高炎症标志物的患者中，应考虑DADA 2。
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.