Objectives: DISH/CC is a poorly understood phenotype
characterised by peripheral and axial enthesopathic
calcifications, frequently fulfilling the radiological
criteria for Diffuse Idiopathic Skeletal Hyperostosis
(DISH, MIM 106400), and in some cases associated
with Calcium Pyrophosphate Dihydrate (CPPD) Chondrocalcinosis
(CC). The concurrence of DISH and CC
suggests a shared pathogenic mechanism. In order to
identify genetic variants for susceptibility we performed
whole exome sequencing in four patients showing this
phenotype.
Materials and methods: Exome data were filtered in
order to find a variant or a group of variants that could
be associated with the DISH/CC phenotype. Variants
of interest were subsequently confirmed by Sanger sequencing.
Selected variants were screened in a cohort
of 65 DISH/CC patients vs 118 controls from Azores.
The statistical analysis was performed using PLINK
V1.07.
Results:We identified 21 genetic variants in 17 genes
that were directly or indirectly related to mineralization,
several are predicted to have a strong effect at a
protein level. Phylogenetic analysis of altered amino
acids indicates that these are either highly conserved
in vertebrates or conserved in mammals. In case-control
analyses, variant rs34473884 in PPP2R2D was significantly
associated with the DISH/CC phenotype
(p=0.028; OR=1.789, 95% CI= 1.060 - 3.021)).
Conclusion: The results of the present and preceding
studies with the DISH/CC families suggests that the
phenotype has a polygenic basis. The PPP2R2D gene could be involved in this phenotype in an as yet unknown way.FRCT: M3.1.2/F/023/2011info:eu-repo/semantics/publishedVersio
