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THU0015 Genetic Analyses of Candidate Genes for Sapho Syndrome
  1. F. J Del Castillo1,2,
  2. L. Ruiz-Palmero1,2,
  3. M. Hurtado-Nédélec3,
  4. T. Caniego1,2,
  5. M. F. Kahn4,
  6. E. Gómez-Rosas1,2,
  7. O. Meyer4,
  8. S. Chollet-Martin3,
  9. G. Hayem4
  1. 1Unidad de Genética Molecular, Hospital Universitario Ramón y Cajal, IRYCIS
  2. 2Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
  3. 3Département d’Hématologie et d’Immunologie biologique
  4. 4Service de Rhumatologie, CHU Bichat-Claude Bernard, Paris, France


Background The Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO) syndrome is currently considered as an autoinflammatory disorder of bone and skin that can be classified with the inflammatory spondyloarthropathies (1). Genetic predisposing factors for SAPHO syndrome have been long suspected because of reported familial clustering of the syndrome, although most cases are sporadic (2). Additional support for a genetic origin of the syndrome is provided by a murine model (the cmo mouse) that carries a spontaneous recessive mutation in the Pstpip2 gene (3). However, previous studies excluded a role for the genes PSIPT2, LPIN and NOD2 in the pathogenesis of the syndrome (4). Two rare autoinflammatory disorders, DIRA and DITRA syndromes, have been related to a genetic deficiency in interleukin-1 (IL-1) and IL-36 receptor antagonists, respectively (5-7). These two conditions, particularly DIRA syndrome, share some features with SAPHO syndrome.

Objectives We investigated the possible role of the genes encoding IL-1 receptor antagonist (IL1RN), IL-36 receptor (IL36R), IL-36 receptor antagonist (IL36RN) and cell-surface lectin Siglec-15 (SIGLEC15) in the pathogenesis of SAPHO syndrome.

Methods The study was performed on a cohort of 40 SAPHO syndrome subjects that includes 3 familial cases. After obtaining written informed consent, we extracted DNA from peripheral blood samples by using automated magnetic-bead technology (Chemagen). We PCR-amplified and sequenced all exons and intron-exon boundaries of the four candidate genes. In addition, we carried out a genome-wide copy-number variation (CNV) analysis on SNP arrays (Illumina BeadStudio array of 2.5 million SNPs).

Results We did not identify any pathogenic mutations in the IL1RN, IL36R, IL36RN and SIGLEC15 genes, although we did detect known polymorphic variations. Heterozygosity and CNV analyses excluded any deletions of the candidate genes in our cohort.

Conclusions We found no involvement of the IL1RN, IL36R, IL36RN and SIGLEC15 genes in the pathogenesis of SAPHO syndrome.


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Acknowledgements T.C. was a recipient of an “Ayuda Predoctoral” fellowship from CIBERER. This work was supported by grant FIS PI11/00283 from ISCIII (to F.J.d.C.).

Disclosure of Interest None Declared

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