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Background and purpose: The aim was to define the radiological picture of facioscapulohumeral muscular dystrophy 2 (FSHD2) in comparison with FSHD1 and to explore correlations between imaging and clinical/molecular data. Methods: Upper girdle and/or lower limb muscle magnetic resonance imaging scans of 34 molecularly confirmed FSHD2 patients from nine European neuromuscular centres were analysed. T1‐weighted and short‐tau inversion recovery (STIR) sequences were used to evaluate the global pattern and to assess the extent of fatty replacement and muscle oedema. Results: The most frequently affected muscles were obliquus and transversus abdominis, semimembranosus, soleus and gluteus minimus in the lower limbs; trapezius, serratus anterior, latissimus dorsi and pectoralis major in the upper girdle. Iliopsoas, popliteus, obturator internus and tibialis posterior in the lower limbs and subscapularis, spinati, sternocleidomastoid and levator scapulae in the upper girdle were the most spared. Asymmetry and STIR hyperintensities were consistent features. The pattern of muscle involvement was similar to that of FSHD1, and the combined involvement of trapezius, abdominal and hamstring muscles, together with complete sparing of iliopsoas and subscapularis, was detected in 91% of patients. Peculiar differences were identified in a rostro‐caudal gradient, a predominant involvement of lower limb muscles compared to the upper girdle, and in the higher percentage of STIR hyperintensities in FSHD2. Conclusion: This multicentre study defines the pattern of muscle involvement in FSHD2, providing useful information for diagnostics and clinical trial design. Both similarities and differences between FSHD1 and FSHD2 were detected, which is also relevant to better understand the pathogenic mechanisms underlying the FSHD‐related disease spectrum. [ABSTRACT FROM AUTHOR]

The case of a 24‐year‐old male patient affected by follicular occlusion tetrad (acne conglobata, hidradenitis suppurativa, pilonidal cyst and dissecting cellulitis of the scalp) associated with clinical signs of pachyonychia congenita (PC)‐2 (focal palmoplantar keratoderma, plantar pain, onycodystrophy and multiple cysts) is reported. The diagnosis was supported by genetic analysis that showed heterozygous mutation within the exon 1 of KRT17 gene. This case may reflect different expressions of a phenotypic spectrum induced by a common genetic alteration. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Non-parametric linkage analyses have mapped many susceptibility loci on different chromosomes. We mapped one of these loci,PSORS4, on human chromosome 1q21. Using the linkage disequilibrium approach, we refined the critical region to a specific genomic interval of about 100 Kb which contains only the loricrin (LOR) gene. Here we report a genetic and functional study of this gene to verify its involvement in psoriasis pathogenesis. We document low expression ofLORin psoriatic skin of patients selected from families in which the disease was segregrating with thePSORS4locus. Re-sequencing of the entire gene in a subset of patients revealed the existence of novel polymorphisms able to influence the protein structure, as shown by molecular modelling studies. However, no evidence for genetic association was detected in a large cohort of Italian nuclear families. This rules out theLORgene as a candidate for thePSORS4locus. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study of gonadal mosaicism in hereditary angioneurotic edema (HAE), a rare autosomal dominant disorder resulting from the congenital deficiency of functional C1 esterase inhibitor protein. Symptoms of HAE include recurrent episodes of swelling of the extremities, face, trunk, airways or abdominal viscera. A description of the experimental setup and measurement method is given. The study concludes that the presence of germline mosaicism must be considered in all cases of angioedema.

Psoriasis and psoriatic arthritis are multifactorial chronic disorders whose etiopathogenesis essentially derives from the alteration of several signalling pathways and the co-occurrence of genetic, epigenetic and non-genetic susceptibility factors that altogether affect the functional and structural property of the skin. Although shared and differential susceptibility genes and molecular pathways are known to contribute to the onset of pathological phenotypes, further research is needed to dissect the molecular causes of psoriatic disease and its progression towards Psoriatic Arthritis. This review will therefore be addressed to explore differences and similarities in the etiopathogenesis and progression of both disorders, with a particular focus on genes involved in the maintenance of the skin structure and integrity (keratins and collagens), modulation of patterns of recognition (through Toll-like receptors and dectin-1) and immuno-inflammatory response (by NLRP3-dependent inflammasome) to microbial pathogens. In addition, special emphasis will be given to the contribution of epigenetic elements (methylation pattern, non-coding RNAs, chromatin modifiers and 3D genome organization) to the etiopathogenesis and progression of psoriasis and psoriatic arthritis. The evidence discussed in this review highlights how the knowledge of patients' clinical and (epi)genomic make-up could be helpful for improving the available therapeutic strategies for psoriasis and psoriatic arthritis treatment., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: Psoriatic arthritis (PsA) is a common inflammatory joint disease distinct from other chronic arthritides and frequently accompanied by psoriasis vulgaris. In a first genome-wide association study (GWAS), we were able to identify several genetic risk factors. However, even combined with previously identified factors, the genetic contribution to disease was not fully explained. Therefore, we undertook this study to investigate further 17 loci from our GWAS that did not reach genome-wide significance levels of association in the initial analysis., Methods: Twenty-one of 22 single-nucleotide polymorphisms were successfully genotyped in independent cohorts of 1,398 PsA patients and 6,389 controls and in a group of 964 German patients with psoriasis vulgaris., Results: Association with a RUNX3 variant, rs4649038, was replicated in independent patients and controls and resulted in a combined P value of 1.40 × 10(-8) by Cochran-Mantel-Haenszel test and an odds ratio (OR) of 1.24 (95% confidence interval [95% CI] 1.15-1.33). Further analyses based on linkage disequilibrium (LD) at RUNX3 refined the most significant association to an LD block located in the first intron of one isoform. Weaker evidence for association was detected in German patients with psoriasis vulgaris (P = 5.89 × 10(-2) ; OR 1.13 [95% CI 1.00-1.28]), indicating a role in the skin manifestations of psoriasis., Conclusion: Our analyses identified variants in RUNX3 as susceptibility factors for PsA. RUNX3 has already been implicated in susceptibility to ankylosing spondylitis, another spondyloarthritis, although its risk allele is independent from the one for PsA. RUNX-3 is involved in CD8+ T lymphocyte differentiation and is therefore a good candidate for involvement in PsA and psoriasis vulgaris as T cell-mediated diseases., (Copyright © 2013 by the American College of Rheumatology.)

Objective: The strongest susceptibility locus of psoriatic arthritis (PsA) is within the major histocompatibility complex (MHC) region (psoriasis susceptibility region 1, or PSORS1), and HLA-Cw*06:02 has been reported as the PSORS1 susceptibility allele. Non-HLA genes within the MHC region have also been implicated in PsA, but because of the strong linkage disequilibrium at chromosome 6p21, it is difficult to make a distinction between susceptibility alleles and linked markers. Recent studies have demonstrated that the association between PsA and the tumor necrosis factor (TNF) promoter polymorphism TNF*-857 is independent of PSORS1. The aim of this study was to replicate the independent association of TNF*-857 in patients with PsA., Methods: A total of 909 patients with PsA and 1,315 healthy controls originating from the UK, Germany, and Italy were typed for TNF*-857 and for the estimated risk alleles of HLA-Cw*06:02., Results: Overall, the results of genotyping in these 3 case-control cohorts replicated the finding that the frequency of carriers of TNF*-857 TT/CT who were negative for the PSORS1 risk allele was significantly higher among patients with PsA compared with control subjects (30% versus 21%; P = 9.17 × 10(-5))., Conclusion: The results of this collaborative study indicate that TNF*-857T is a susceptibility allele for PsA independent of the PSORS1 allele., (Copyright © 2011 by the American College of Rheumatology.)

Objective: The LCE3C_LCE3B-del variant is associated with psoriasis and rheumatoid arthritis. Its role in psoriatic arthritis (PsA) is unclear, however, as shown by 3 recent studies with contradictory results. In order to investigate whether LCE3C_LCE3B-del constitutes a risk factor for PsA susceptibility, we first tested this variant in patients with PsA from Spanish and Italian populations and then performed a meta-analysis including the previous case-control studies., Methods: We genotyped LCE3C_LCE3B-del and its tag single-nucleotide polymorphism (SNP), rs4112788, in an original discovery cohort of 424 Italian patients with PsA and 450 unaffected control subjects. A Spanish replication cohort consisting of 225 patients with PsA and 469 control subjects was also genotyped. A meta-analysis considering 7,758 control subjects and 2,325 patients with PsA was also performed., Results: We observed a significant association between PsA and the LCE3C_LCE3B-del tag SNP in the Italian and Spanish cohorts, with an overall corrected P value of 0.00019 and a corresponding odds ratio of 1.35 (95% confidence interval 1.14-1.59). Stratified analyses by subphenotype indicated a stronger association for patients with oligoarticular disease. Meta-analysis including data from all previous published studies confirmed an association of PsA with the LCE3C_LCE3B-del tag SNP., Conclusion: LCE3C_LCE3B-del is a susceptibility factor for PsA, confirming the existence of a shared risk factor involving the epidermal skin barrier in autoimmune disorders., (Copyright © 2011 by the American College of Rheumatology.)

Objective: Subclinical gut inflammation is common in spondylarthritis, but the immunologic abnormalities underlying this process are undefined. Perturbation of the interleukin-23 (IL-23)/Th17 axis has emerged as a fundamental trigger of chronic inflammation. This study was undertaken to investigate the expression and tissue distribution of IL-23/Th17-related molecules in Crohn's disease (CD) and in subclinical gut inflammation in ankylosing spondylitis (AS)., Methods: Quantitative gene expression analysis of Th1/Th2 and IL-23/Th17 responses was performed in intestinal biopsy samples obtained from 12 patients with CD, 15 patients with AS, and 13 controls. IL-23 tissue distribution and identification of IL-23-producing cells were evaluated by immunohistochemistry., Results: We demonstrated a strong and significant up-regulation of IL-23p19 transcripts in the terminal ileum in patients with AS and patients with CD. IL-23 was abundantly produced by infiltrating monocyte-like cells in inflamed mucosa from AS and CD patients. Notably, we also identified Paneth cells as a major source of IL-23 in patients with AS, patients with CD, and normal controls. Unlike CD, in AS patients, IL-23 was not associated with up-regulation of IL-17 and the IL-17-inducing cytokines IL-6 and IL-1beta. Finally, while the Th1-related cytokines interferon-gamma, IL-12p35, and IL-27p28 were overexpressed only in CD patients, IL-4, IL-5, and STAT-6 were also significantly increased in AS patients., Conclusion: Our findings indicate that overexpression of IL-23, but not IL-17, is a pivotal feature of subclinical gut inflammation in AS. Identification of resident Paneth cells as a pivotal source of IL-23 in physiologic and pathologic conditions strongly suggests that IL-23 is a master regulator of gut mucosal immunity, providing a pathophysiologic significance to the reported association between IL-23 receptor polymorphisms and intestinal inflammation.