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.
Institute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Kiel, Germany.
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S
Bens
European Molecular Biology Laboratory (EMBL), Genome Biology Research Unit, Heidelberg, Germany.
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T
Zichner
European Molecular Biology Laboratory (EMBL), Genome Biology Research Unit, Heidelberg, Germany.
A M
AM
Stütz
Institute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Kiel, Germany.
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A
Caliebe
Institute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Kiel, Germany.
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R
Wagener
1] Institute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Kiel, Germany [2] Department of Congenital Heart Disease and Pediatric Cardiology, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Kiel, Germany.
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K
Hoff
European Molecular Biology Laboratory (EMBL), Genome Biology Research Unit, Heidelberg, Germany.
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JO
Korbel
Department of Pediatrics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Kiel, Germany.
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P
von Bismarck
Institute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Kiel, Germany.
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R
Siebert
D000954:Antigens, Surface / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D056905:Chromosome Breakpoints; D005260:Female; D005334:Fever / Q000235:genetics*; D056726:Genetic Association Studies; D057895:Haploinsufficiency; D006801:Humans; D007223:Infant; D007621:Karyotyping; D008206:Lymphatic Diseases / Q000235:genetics*; D008297:Male; D010612:Pharyngitis / Q000235:genetics*; D013281:Stomatitis, Aphthous / Q000235:genetics*; D013577:Syndrome; D014178:Translocation, Genetic
D000954:Antigens, Surface; C000593329:SPAG7 protein, human