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SPAG7 is a candidate gene for the periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome


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.

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We thank the technical staff of the cytogenetic and molecular genetic laboratories of the Institute of Human Genetics for expert assistance, as well as all clinicians involved in the care of the patients for support and all individuals for their participation. JOK was supported by an Emmy Noether Fellowship (KO 4037/1-1) from the German Research Foundation and RW is recipient of a stipend from the KinderKrebsInitiative Buchholz/Holm-Seppensen. RS is a member of the Excellence Cluster ‘Inflammation at Interfaces’.

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Correspondence to S Bens.

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Bens, S., Zichner, T., Stütz, A. et al. SPAG7 is a candidate gene for the periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome. Genes Immun 15, 190–194 (2014).

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  • SPAG7
  • periodic fever
  • chromosomal translocation

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