A phenotype characterized by age-dependent hairless, thicker and systemic wrinkled skin has been discovered from Chinese native Xiang pig herd, which is similar to the wrinkle skin phenotype and hereditary periodic fever syndrome observed in Shar-Pei dog. Our aim was to elucidate the functional mechanisms associated with these systemic wrinkle phenotype. Gene expression changes in wrinkled skin were first explored via RNA-seq technology. There were 699 differentially expressed genes (DEGs) in wrinkled skin, with 272 downregulated genes and 427 upregulated genes. Most of the upregulated genes were significantly centered at pathways that generate reactive oxygen species (ROS), such as carbon and lipid metabolism, the citrate cycle and the oxidation-reduction process, leading to excessive ROS production and/or DNA damage in both the epidermal and dermal compartments of the skin. The downregulated genes were involved mainly in extracellular matrix (ECM) signaling. The most decreased genes were focused on several ECM components, including COL1A1, COL21A1, COL6A3, and ELN, likely related with ECM disorders. Moreover, 831 SVs and 26 CNVs were found in the gene regions of 335 DEGs according to the genomic resequencing data from the same wrinkled skin and control samples. These SVs and CNVs contributed to the deletion, insertion, duplication and inversion in exons, introns and regulatory regions of the DEGs. We then used F2 crossbreds by using Large White pig and the wrinkled Xiang pig as parents to verify the skin features and gene expression changes. Approximately 26% of F2 individuals exhibited a wrinkled skin phenotype, whereas the skin on F1 hybrids remained unchanged, suggesting autosomal recessive inheritance. The disorganized and thinner collagen bundles in the dermis of wrinkled skin were very similar to those of the parents, and many genes were shared between F2 pigs and the parents, including 137 DEGs corresponding to wrinkle scores, 23 oxidative stress-related genes, nine aging-related genes, and four ECM genes. The systemic wrinkled skin phenotype of pigs involves aberrant gene expression and genetic variations related to oxidative stress and ECM components.

Though the incidence of familial Mediterranean fever (FMF) in pregnancy is rare, understanding the etiology and symptomatology of FMF is essential for obstetric treatment of patients with FMF. Familial Mediterranean fever is a hereditary periodic fever syndrome that has unique obstetric considerations. Familial Mediterranean fever is typically characterized by recurrent episodes of high-grade fevers, pleuritis/pericarditis, and arthritis lasting 1-3 days with complete recovery seen in between episodes. Familial Mediterranean fever is seen worldwide, but particularly in patients of Mediterranean descent. Its incidence varies across ethnicities. This article provides a comprehensive review of existing literature. It is well established that colchicine is safe and effective to use during pregnancy in patients with FMF to control and prevent flares. Although most pregnancies progress without negative outcomes, FMF has been shown in the literature to be associated with preterm birth and premature rupture of membranes. Its impact on increasing the rate of fetal growth restriction and hypertensive disorders is less understood. Additionally, FMF flares may be suppressed in pregnancy, whereas other sources report that flares are similar to those outside of pregnancy in terms of frequency, type of symptoms, and severity. Breastfeeding is safe in patients with FMF who are taking colchicine. Genetic counseling can be offered to patients with FMF, but in utero diagnostic testing is generally not pursued solely for the indication of FMF diagnosis in the fetus. Further investigation of the impact of FMF on pregnancy is needed for advancing our understanding of the condition and optimizing care for pregnant individuals with FMF.

Through continuous innovation and improvement, Nanopore sequencing has become a powerful technology. Because of its fast processing time, low cost, and ability to generate long reads, this sequencing technique would be particularly suitable for clinical diagnostics. However, its raw data accuracy is inferior in contrast to other sequencing technologies. This constraint still results in limited use of Nanopore sequencing in the field of clinical diagnostics and requires further validation and IVD certification. We evaluated the performance of latest Nanopore sequencing in combination with a dedicated data-analysis pipeline for single nucleotide polymorphism (SNP) genotyping of the familial Mediterranean fever gene (MEFV) by amplicon sequencing of 47 clinical samples. Mutations in MEFV are associated with Mediterranean fever, a hereditary periodic fever syndrome. Conventional Sanger sequencing, which is commonly applied in clinical genetic diagnostics, was used as a reference method. Nanopore sequencing enabled the sequencing of 10 target regions within MEFV with high read depth (median read depth 7565x) in all samples and identified a total of 435 SNPs in the whole sample collective, of which 29 were unique. Comparison of both sequencing workflows showed a near perfect agreement with no false negative calls. Precision, Recall, and F1-Score of the Nanopore sequencing workflow were > 0.99, respectively. These results demonstrated the great potential of current Nanopore sequencing for application in clinical diagnostics, at least for SNP genotyping by amplicon sequencing. Other more complex applications, especially structural variant identification, require further in-depth clinical validation.

The study aims are to describe the activity of our Unit on the diagnostics of monogenic autoinflammatory diseases (AIDs), and to apply the clinical classification criteria for periodic fevers from the Eurofever Registry to our cohort of patients, thus evaluating their usefulness in the real life. We retrospectively analyzed data from patients referring to our Center for recurrent fever attacks, and undergoing genetic analysis between April 2014 and July 2016, and we applied the classification criteria to both genetically positive and -negative patients. We visited 195 patients (101 females, 94 males); 126 (64.6%) were adults and 192 (98.5%) Caucasians; 12.3% carried mutations and 12.7% of adults were genetically positive. No statistically significant differences were identified in the frequency of genetic diagnosis between adults and children (p = 0.82) as well as in the frequency of genetic diagnosis, based on the number of genes evaluated (p = 0.57). When we applied the Eurofever criteria, 126/195 (64.6%) patients were classified for at least one among the four main monogenic AIDs; 22 (11.3%) patients fulfilled criteria for 2 diseases and 4 (2.1%) for 3 diseases. Among patients carrying mutations, 12/24 (50%) correctly fulfilled the score, 3/24 (12.5%) fulfilled criteria differently from their genetic diagnosis; 9/22 (40.9%) recieved no classification. An expanded genetic testing does not seem useful, while a correct interpretation of patients' clinical picture may allow performing specific genetic testing. The classification criteria from the Eurofever Registry have shown to be a beneficial tool in the evaluation of patients with a suspected monogenic AID.

In this article, we report a nine-month-old male patient with a history of three unexplained, prolonged attacks of high fever, including one in the neonatal period, accompanied by an erythematosus, migratory rash. There was no family history that might have suggested a hereditary periodic fever syndrome, but the overall clinical picture was in accordance with tumor necrosis factor receptor-associated disease. Genetic analysis revealed two heterozygous mutations: C30Y in the tumor necrosis factor receptor superfamily 1A gene and K695R in the Mediterranean fever gene. This case shows that diagnosis of an autoinflammatory syndrome should be considered even in the youngest infants with incomplete presentation and no family history of recurrent fever.