Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped to an approximately 5.8 Mb region at 12p13.1 but no candidate gene was identified. In an international consortium we recruited 19 independent families comprising 107 individuals with pEDS to identify the locus, characterize the clinical details in those with defined genetic causes, and try to understand the physiological basis of the condition. In 17 of these families, we identified heterozygous missense or in-frame insertion/deletion mutations in C1R (15 families) or C1S (2 families), contiguous genes in the mapped locus that encode subunits C1r and C1s of the first component of the classical complement pathway. These two proteins form a heterotetramer that then combines with six C1q subunits. Pathogenic variants involve the subunit interfaces or inter-domain hinges of C1r and C1s and are associated with intracellular retention and mild endoplasmic reticulum enlargement. Clinical features of affected individuals in these families include rapidly progressing periodontitis with onset in the teens or childhood, a previously unrecognized lack of attached gingiva, pretibial hyperpigmentation, skin and vascular fragility, easy bruising, and variable musculoskeletal symptoms. Our findings open a connection between the inflammatory classical complement pathway and connective tissue homeostasis.

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Purpose Various resin cements and priming agents are available for adhesive luting of zirconia restorations. The purpose of this study was to investigate how cement type and priming protocol affect the shear bond strength on zirconia ceramics. Materials and Methods Yttria‐stabilized tetragonal zirconia polycrystalline ceramic cylinders were bonded to flat zirconia ceramic surfaces using 7 commercially available resin cements. Ten specimens of each cement group were pretreated with a universal primer, and 10 specimens per group were bonded without pretreatment. In addition, 10 specimens per group were pretreated with system‐specific zirconia primers, which were available for 3 cements. Altogether, 170 bonded specimens were water‐stored, thermal‐cycled, and then submitted to shear bond strength tests. The shear bond strength and the fracture types were documented. Differences in shear bond strengths were assessed using 2‐way ANOVA with post‐hoc test (α = 0.05). A point‐biserial correlation was run between the fracture patterns and the shear bond strengths. Results The mean shear bond strengths of cements in the unprimed group showed large variations between 2.52 ± 3.01 (mean ± SD) MPa and 33.15 ± 7.35 MPa. Pretreating the specimens with a universal primer improved the shear bond strengths significantly in all groups (p < 0.05) with a range of 21.80 ± 12.51 to 57.20 ± 11.40 MPa. The system‐specific primers also improved the shear bond strength significantly, compared to the unprimed group (p < 0.01); however, only one system‐specific primer achieved a shear bond strength superior to the universal primer (p < 0.01). There was also a statistical correlation between the fracture type and the shear bond strength (p < 0.0005), with cohesively fractured specimens showing higher shear bond strengths (37.24 ± 19.87 MPa) than adhesively fractured specimens (23.10 ± 17.65 MPa) (p < 0.001). Conclusion Using universal primer can enhance the maximal shear bond strength of zirconia.