Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Pediatric Department A, Pediatric Immunology Service, "Edmond and Lily Safra" Children's Hospital, Jeffrey Modell Foundation (JMF) Center, Tel HaShomer, Israel.
Pediatr Blood Cancer. 2020 Jun;67(6):e28237. doi: 10.1002/pbc.28237. Epub 2020 Apr 11.
The SRP54 (signal recognition protein 54) is a conserved component of the ribonucleoprotein complex that mediates cotranslational targeting and translocation of proteins to the endoplasmic reticulum. In 2017, mutations in the gene have been described as a cause of congenital neutropenia with or without pancreatic insufficiency, and since then, only limited cases were added to the literature.
Two patients with neutropenia underwent hematological, immunological, and genetic work-up, including lymphocyte phenotyping, immunoglobulins, and complement levels, antineutrophil and antinuclear antibodies, bone marrow FISH panel for myelodysplastic syndrome, whole-exome sequencing, and in silico proteomic analysis.
Clinical findings in the two families revealed a wide spectrum of immunological and clinical manifestations, ranging from mild asymptomatic neutropenia during febrile illnesses to severe neutropenia and life-threatening infection requiring leg amputation. Immunological and hematological work-up showed isolated neutropenia with normal lymphocyte subpopulations, immunoglobulin and complement levels, and negative autoimmune tests. Bone marrow aspirations showed variability ranging from normal myelopoiesis to myeloid maturation arrest at the promyelocytic stage, with normal FISH panel for myelodysplastic syndrome. Genetic analysis identified a novel, de novo, in-frame deletion in the SRP54 gene, c.342-344delAAC, p.T115del. In silico proteomic analysis suggested impaired SRP54 protein function due to reduced GTP activity and stability.
We describe congenital neutropenia with variable clinical presentation in novel mutation of the SRP54 gene.
SRP54（信号识别蛋白 54）是核糖核蛋白复合物的保守成分，介导蛋白质共翻译靶向和易位到内质网。2017 年，该基因的突变被描述为伴有或不伴有胰腺功能不全的先天性中性粒细胞减少症的原因，此后，文献中仅增加了有限数量的病例。
两名中性粒细胞减少症患者接受了血液学、免疫学和遗传学检查，包括淋巴细胞表型、免疫球蛋白和补体水平、抗中性粒细胞和抗核抗体、骨髓 FISH .panel 用于骨髓增生异常综合征、外显子组测序和计算蛋白质组学分析。
两个家族的临床发现显示出广泛的免疫和临床表现谱，从发热时无症状的轻度中性粒细胞减少症到严重的中性粒细胞减少症和危及生命的感染需要截肢不等。免疫和血液学检查显示孤立性中性粒细胞减少症，伴有正常的淋巴细胞亚群、免疫球蛋白和补体水平以及阴性自身免疫试验。骨髓抽吸显示从正常髓系生成到早幼粒细胞阶段的髓系成熟停滞的变异性，骨髓 FISH.panel 正常用于骨髓增生异常综合征。基因分析确定了 SRP54 基因中的一种新的、从头的、框内缺失，c.342-344delAAC，p.T115del。计算蛋白质组学分析表明由于 GTP 活性和稳定性降低，SRP54 蛋白功能受损。
我们描述了具有可变临床表现的先天性中性粒细胞减少症，这是 SRP54 基因的新突变。
