PRF1、MUNC13-4 和 STXBP2 的功能获得性突变与成人发病的家族性 HLH 相关。
Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH.
机构信息
Division of Human Genetics, Children's Hospital Medical Center, University of Cincinnati College of Medicie, Cincinnati, OH 45229, USA.
出版信息
Blood. 2011 Nov 24;118(22):5794-8. doi: 10.1182/blood-2011-07-370148. Epub 2011 Aug 31.
Abstract
Familial hemophagocytic lymphohistiocytosis (HLH) is a rare primary immunodeficiency disorder characterized by defects in cell-mediated cytotoxicity that results in fever, hepatosplenomegaly, and cytopenias. Familial HLH is well recognized in children but rarely diagnosed in adults. We conducted a retrospective review of genetic and immunologic test results in patients who developed HLH in adulthood. Included in our study were 1531 patients with a clinical diagnosis of HLH; 175 patients were 18 years or older. Missense and splice-site sequence variants in PRF1, MUNC13-4, and STXBP2 were found in 25 (14%) of the adult patients. The A91V-PRF1 genotype was found in 12 of these patients (48%). The preponderance of hypomorphic mutations in familial HLH-causing genes correlates with the later-onset clinical symptoms and the more indolent course in adult patients. We conclude that late-onset familial HLH occurs more commonly than was suspected previously.
摘要
家族性噬血细胞性淋巴组织细胞增生症（HLH）是一种罕见的原发性免疫缺陷病，其特征是细胞介导的细胞毒性缺陷，导致发热、肝脾肿大和细胞减少症。家族性 HLH 在儿童中得到很好的认识，但在成人中很少被诊断。我们对成年后发生 HLH 的患者进行了基因和免疫检测结果的回顾性分析。我们的研究包括了 1531 名临床诊断为 HLH 的患者，其中 175 名患者年龄在 18 岁或以上。在 25 名成年患者（14%）中发现了 PRF1、MUNC13-4 和 STXBP2 中的错义突变和剪接位点序列变异。在这些患者中，发现了 12 名患者（48%）存在 A91V-PRF1 基因型。家族性 HLH 致病基因中的低功能突变与成年患者发病较晚、症状更隐匿、病程更迁延的特点相关。我们的结论是，晚发性家族性 HLH 比以前怀疑的更为常见。
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