Next Generation Sequencing and Electromyography Reveal the Involvement of the P2RX6 Gene in Myopathy.

Ion channelopathies result from impaired ion channel protein function, due to mutations affecting ion transport across cell membranes. Over 40 diseases, including neuropathy, pain, migraine, epilepsy, and ataxia, are associated with ion channelopathies, impacting electrically excitable tissues and significantly affecting skeletal muscle. Gene mutations affecting transmembrane ionic flow are strongly linked to skeletal muscle disorders, particularly myopathies, disrupting muscle excitability and contraction. Electromyography (EMG) analysis performed on a patient who complained of weakness and fatigue revealed the presence of primary muscular damage, suggesting an early-stage myopathy. Whole exome sequencing (WES) did not detect potentially causative variants in known myopathy-associated genes but revealed a novel homozygous deletion of the P2RX6 gene likely disrupting protein function. The P2RX6 gene, predominantly expressed in skeletal muscle, is an ATP-gated ion channel receptor belonging to the purinergic receptors (P2RX) family. In addition, STRING pathways suggested a correlation with more proteins having a plausible role in myopathy. No previous studies have reported the implication of this gene in myopathy. Further studies are needed on patients with a defective ion channel pathway, and the use of in vitro functional assays in suppressing P2RX6 gene expression will be required to validate its functional role.

STXBP6 Gene Mutation: A New Form of SNAREopathy Leads to Developmental Epileptic Encephalopathy.

Syntaxin-binding protein 6 (STXBP6), also known as amysin, is an essential component of the SNAP receptor (SNARE) complex and plays a crucial role in neuronal vesicle trafficking. Mutations in genes encoding SNARE proteins are often associated with a broad spectrum of neurological conditions defined as "SNAREopathies", including epilepsy, intellectual disability, and neurodevelopmental disorders such as autism spectrum disorders. The present whole exome sequencing (WES) study describes, for the first time, the occurrence of developmental epileptic encephalopathy and autism spectrum disorders as a result of a de novo deletion within the STXBP6 gene. The truncated protein in the STXBP6 gene leading to a premature stop codon could negatively modulate the synaptic vesicles' exocytosis. Our research aimed to elucidate a plausible, robust correlation between STXBP6 gene deletion and the manifestation of developmental epileptic encephalopathy.

Phytochemical Characterization and In Vitro Antioxidant Properties of Four Brassica Wild Species from Italy.

In the present study, we evaluated for the first time the variability of antioxidant traits of four Brassica wild species: B. incana, B. macrocarpa, B. villosa, and B. rupestris. The content of the main water-soluble antioxidants (phenolics, ascorbic acid, and total biothiols) and the in vitro antioxidant potential (1,1-diphenyl-2-picrylhydrazil (DPPH) and superoxide anion scavenging capacity) were investigated. A total of 28 polyphenolic compounds were identified by LC/MS and quantitated by HPLC/DAD analysis. Kaempferol and quercetin derivatives were the most abundant phenolics compared to hydroxycinnamoyl gentiobiosides. In the ten populations, phenolics ranged from 163.9 to 533.9 mg/100 g dry weight (d.w.), ascorbic acid from 7.6 to 375.8 mg/100 g d.w., and total biothiols from 0.59 to 5.13 mg/100 g d.w. The different classes of phytochemicals were separated using solid-phase extraction at increasing methanol concentrations, and the antioxidant power of fractionated extracts was evaluated. The superoxide anion scavenging activity was significantly correlated to phenolics, particularly to flavonol derivatives, while DPPH was mainly related to ascorbic acid content. The present findings improve the knowledge of the phytochemical composition of Italian Brassica wild species by showing the great diversity of phytochemicals among populations and highlighting their importance as a valuable genetic resource for developing new cultivars with improved bioactive content.

UNC5C: Novel Gene Associated with Psychiatric Disorders Impacts Dysregulation of Axon Guidance Pathways.

The UNC-5 family of netrin receptor genes, predominantly expressed in brain tissues, plays a pivotal role in various neuronal processes. Mutations in genes involved in axon development contribute to a wide spectrum of human diseases, including developmental, neuropsychiatric, and neurodegenerative disorders. The NTN1/DCC signaling pathway, interacting with UNC5C, plays a crucial role in central nervous system axon guidance and has been associated with psychiatric disorders during adolescence in humans. Whole-exome sequencing analysis unveiled two compound heterozygous causative mutations within the UNC5C gene in a patient diagnosed with psychiatric disorders. In silico analysis demonstrated that neither of the observed variants affected the allosteric linkage between UNC5C and NTN1. In fact, these mutations are located within crucial cytoplasmic domains, specifically ZU5 and the region required for the netrin-mediated axon repulsion of neuronal growth cones. These domains play a critical role in forming the supramodular protein structure and directly interact with microtubules, thereby ensuring the functionality of the axon repulsion process. We emphasize that these mutations disrupt the aforementioned processes, thereby associating the UNC5C gene with psychiatric disorders for the first time and expanding the number of genes related to psychiatric disorders. Further research is required to validate the correlation of the UNC5C gene with psychiatric disorders, but we suggest including it in the genetic analysis of patients with psychiatric disorders.

Molecular Markers for Detecting Inflorescence Size of Brassica oleracea L. Crops and B. oleracea Complex Species (n = 9) Useful for Breeding of Broccoli (B. oleracea var. italica) and Cauliflower (B. oleracea var. botrytis).

The gene flow from Brassica oleracea L. wild relatives to B. oleracea vegetable crops have occurred and continue to occur ordinarily in several Mediterranean countries, such as Sicily, representing an important hot spot of diversity for some of them, such as broccoli, cauliflower and kale. For detecting and for exploiting the forgotten alleles lost during the domestication processes of the B. oleracea crops, attention has been pointed to the individuation of specific markers for individuating genotypes characterized by hypertrophic inflorescence traits by the marker assisted selection (MAS) during the first plant growing phases after the crosses between broccoli (B. oleracea var. italica)/cauliflower (B. oleracea var. botrytis) with B. oleracea wild relatives (n = 9), reducing the cultivation and evaluation costs. The desired traits often found in several B. oleracea wild relatives are mainly addressed to improve the plant resistance to biotic and abiotic stresses and to increase the organoleptic, nutritive and nutraceutical traits of the products. One of the targeted traits for broccoli and cauliflower breeding is represented by the inflorescences size as is documented by the domestication processes of these two crops. Based on the previous results achieved, the numerical matrix, obtained utilizing five simple sequence repeats (SSRs), was analyzed to assess the relationship among the main inflorescence characteristics and the allelic variation of the SSRs loci analyzed (BoABI1, BoAP1, BoPLD1, BoTHL1 and PBCGSSRBo39), both for the Brassica oleracea and B. oleracea wild relatives (n = 9) accessions set. The main inflorescence morphometric characteristics, such as weight, height, diameter, shape, inflorescence curvature angle and its stem diameter, were registered before the flower anthesis. We analyzed the correlations among the allelic variation of the SSRs primers utilized and the inflorescence morphometric characteristics to individuate genomic regions stimulating the hypertrophy of the reproductive organ. The relationships found explain the diversity among B. oleracea crops and the B. oleracea complex species (n = 9) for the inflorescence size and structure. The individuated markers allow important time reduction during the breeding programs after crossing wild species for transferring useful biotic and abiotic resistances and organoleptic and nutraceutical traits to the B. oleracea crops by MAS.