BACKGROUND: Cryopyrin-associated periodic syndrome (CAPS), a rare genetic autoimmune disease, is composed of familial cold autoinflammatory syndrome (FCAs), Muckle-Wells syndrome (MWS), and neonatal onset multisystem inflammatory disease (NOMID). MWS is caused by dominantly inherited or de novo gain-of-function mutations in the NOD-like receptor 3 (NLRP3) gene. At present, there is no report about the variation of R262W in China.
METHODS: We reported a 3-year-old Chinese boy who had recurrent fever without obvious inducement, bilateral conjunctival congestion, and urticarial-like rash. Laboratory examination showed elevation in leukocyte count, neutrophil count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) and serum amyloid protein (SAA) levels. Whole exome sequencing identified a missense variation c.784-786delinsTGG (p.R262W) in the coding region of the NLRP3 gene.
CONCLUSIONS: A classical variant of the NLRP3 gene in a patient with MWS was first reported in China.

Non-segmental vitiligo (NSV) is an autoimmune skin disease. Genetics plays a predominant part in disease pathogenesis. Nucleotide-binding and oligomerization domain (NOD)-like receptors and pyrin-containing protein (NLRP) and Toll-like receptors (TLR) are pattern recognition receptors in mediating innate immunity. They participate in presenting pathogens and mediating the immune responses. NLRP and TLRs are involved in mediating immune response in various dermatological diseases. Understanding the influence of genetic polymorphisms of NLRP and TLRs associated with immune homeostasis might help us to understand the complex etiopathogenesis of NSV. Thus, we aimed to study the association of NLRP-1 (rs2670660) and TLR-4 (rs4986790) and the synergistic effects on disease spectrum, disease activity of NSV in South Indian population. This research was designed as a case-control genetic study with 264 patients and 264 controls. Genotyping of NLRP-1 (rs2670660) and TLR-4 (rs4986790) was performed by Taqman 5\' allele discrimination assay and ARMS-PCR. Plasma levels of proteins were measured by enzyme-linked immunosorbent assay (ELISA). A statistically significant difference was observed with the frequency of homozygous GG genotype of NLRP-1 (rs2670660) (17.8% in cases vs. 5.3% in controls) (p < 0.0001; OR-3.73; 95% CI-1.94-7.14). Allele G was significantly frequent in 38% of the cases than in controls with 30% (p = 0.004; OR-1.46; 95% CI-1.13-1.89). Plasma NLRP-1 level was significantly higher in patients compared to controls (p < 0.05). Amongst cases, the plasma NLRP-1 levels did not show any difference with respect to their genotypes (p > 0.05). In TLR-4 (rs4986790), no significant difference in the frequency of genotypes and allele between cases and controls (p = 0.80) was observed; nevertheless, plasma TLR-4 was analogous between cases and controls (p > 0.05). Influence of genotype on plasma TLR-4 showed no significant difference in TLR-4 levels between GG and ancestral genotype AA, whilst heterozygous AG genotype showed a significant increase of TLR-4 compared to AA and GG (p = 0.02) amongst NSV cases. The obtained results suggest that NLRP-1 (rs2670660), and not TLR-4 ((rs4986790), is associated with increased risk of NSV in South Indian population.

BACKGROUND: Hereditary benign intraepithelial dyskeratosis (HBID) is a rare autosomal-dominant disorder of the conjunctiva and oral mucosa first described in and predominantly affecting descendents of Haliwa-Saponi Native Americans. We report a spontaneous case of histopathologically-confirmed HBID affecting an individual not of Native American ancestry.
METHODS: Report of a case with histopathologic examination of an excised conjunctival specimen as well as molecular and cytogenetic analysis.
RESULTS: A Caucasian boy with a history of oral lesions and conjunctival injection from birth developed bilateral corneal opacities at age 5 and underwent penetrating keratoplasty, with recurrence of the corneal opacification shortly after surgery. Examination of a conjunctival biopsy specimen revealed features consistent with HBID. Copy number variant (CNV) analysis revealed a de novo 4q35 duplication that overlapped the duplication previously associated with HBID, although no genes were identified in the common interval. NLRP1 gene sequencing failed to reveal a presumed pathogenic variant.
CONCLUSIONS: HBID may develop de novo in individuals who are not of Native American ancestry. The absence of coding regions in a duplicated region of 4q35 common to both the individual that we report and previously associated with HBID raises questions regarding the significance of this CNV in the pathogenesis of HBID.