Institute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Kiel, Germany.
European Molecular Biology Laboratory (EMBL), Genome Biology Research Unit, Heidelberg, Germany.
Genes Immun. 2014 Apr-May;15(3):190-4. doi: 10.1038/gene.2013.73. Epub 2014 Jan 23.
Periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome is an auto-inflammatory disease for which a genetic basis has been postulated. Nevertheless, in contrast to the other periodic fever syndromes, no candidate genes have yet been identified. By cloning, following long insert size paired-end sequencing, of a de novo chromosomal translocation t(10;17)(q11.2;p13) in a patient with typical PFAPA syndrome lacking mutations in genes associated with other periodic fever syndromes we identified SPAG7 as a candidate gene for PFAPA. SPAG7 protein is expressed in tissues affected by PFAPA and has been functionally linked to antiviral and inflammatory responses. Haploinsufficiency of SPAG7 due to a microdeletion at the translocation breakpoint leading to loss of exons 2-7 from one allele was associated with PFAPA in the index. Sequence analyses of SPAG7 in additional patients with PFAPA point to genetic heterogeneity or alternative mechanisms of SPAG7 deregulation, such as somatic or epigenetic changes.
周期性发热、口疮性口炎、咽炎和淋巴结炎（PFAPA）综合征是一种自身炎症性疾病，其发病基础被认为与遗传因素有关。然而，与其他周期性发热综合征不同的是，目前尚未发现候选基因。通过对一例典型 PFAPA 综合征患者的从头染色体易位 t（10；17）（q11.2；p13）进行克隆，以及长插入片段配对末端测序，我们发现 SPAG7 可能是 PFAPA 的候选基因。SPAG7 蛋白在受 PFAPA 影响的组织中表达，并与抗病毒和炎症反应有关。由于易位断点导致一个等位基因缺失外显子 2-7 的微缺失，SPAG7 出现单倍不足，与索引中的 PFAPA 相关。对其他 PFAPA 患者的 SPAG7 序列分析表明存在遗传异质性或 SPAG7 失调控的其他机制，如体细胞或表观遗传改变。
