BEND4 as a Candidate Gene for an Infection-Induced Acute Encephalopathy Characterized by a Cyst and Calcification of the Pons and Cerebellar Atrophy.

Three siblings born to Turkish parents from the same village had normal brain development until acute neurological deterioration between 12 months and 8 years of age. Consequent loss of all acquired motor, social, and language functions following infections was associated with a pontine cyst, calcification, and cerebellar atrophy. Exome sequencing revealed a homozygous c.1297G>A (p.Gly433Ser) alteration in BEND4, which was predicted to be deleterious in in silico analysis tools and segregated in multiple affected individuals in the family. BEND4 has not been associated with any existing disease. Immunofluorescence microscopy analysis of wild-type and mutant BEND4 expressing Vero cells showed nuclear and cytoplasmic localization. Wild-type BEND4 displayed a network-like distribution, whereas mutant BEND4 showed a juxtanuclear distribution pattern. Differential proteome analysis of Vero cells expressing BEND4 revealed that mutant BEND4 expression caused selective increase in reticulocalbin-1 and endoplasmic reticulum resident protein-29. Both proteins are associated with the endoplasmic reticulum and are primarily involved in protein processing and folding pathways. Any defect or stress in protein folding creates stress on cells and may cause chronic damage. This is the first study showing that pathogenic BEND4 variants may lead to an infection-induced acute necrotizing encephalopathy as demonstrated in characteristic neuroimaging findings.

Abundant proteins in platelet-rich fibrin and their potential contribution to wound healing: An explorative proteomics study and review of the literature.

BACKGROUND/PURPOSE: It is well-known that diverse types of blood proteins contribute to healing process via different mechanisms. Presence and potential involvements of blood-derived abundant proteins in the platelet-rich fibrin (PRF) to its regenerative capacity have not been sufficiently emphasized in the literature. The aim of this paper was to analyze the abundant proteome content of PRF and summarize previously reported effects of identified proteins on wound healing via a literature review. MATERIALS AND METHODS: The PRF samples obtained from non-smoking, systemically healthy volunteers were subjected to 2D gel electrophoresis after extracting the proteins from fibrin matrices. All matching spots were excised from the gels and identified by MALDI TOF/TOF MS/MS analysis. A literature review was conducted to reveal possible contributions of identified proteins to wound healing. RESULTS: Totally, thirty-five blood proteins were commonly identified among all studied samples. These proteins included serine protease inhibitors, such as alpha-1-antitrypsin, alpha-1-antichymotrypsin, alpha-1-acid glycoprotein, inter-alpha-trypsin-inhibitor, protease C1 inhibitor, and complement proteins. In addition, abundant presence of immunoglobulin G was observed. The abundance of albumin, haptoglobin, ceruloplasmin vitronectin, fetuin-A, ficolin-3 and transthyretin was also detected. CONCLUSION: The results of this study indicated that PRF abundantly contains blood-origin actors which were previously reported for their direct contribution to wound healing. Further studies exploring the protein content of PRF are needed to reveal its undisclosed potential roles in the healing process.

Proteomics Analysis of Tissue Samples Reveals Changes in Mitochondrial Protein Levels in Parathyroid Hyperplasia over Adenoma.

BACKGROUND/AIM: To unveil the pathophysiology of primary hyperparathyroidism, molecular details of parathyroid hyperplasia and adenoma have to be revealed. Such details will provide the tools necessary for differentiation of these two look-alike diseases. Therefore, in the present study, a comparative proteomic study using postoperative tissue samples from the parathyroid adenoma and parathyroid hyperplasia patients was performed. MATERIALS AND METHODS: Protein extracts were prepared from tissue samples (n=8 per group). Protein pools were created for each group and subjected to DIGE and conventional 2DE. Following image analysis, spots representing the differentially regulated proteins were excised from the and used for identification via MALDI-TOF/TOF analysis. RESULTS: The identities of 40 differentially-expressed proteins were revealed. Fourteen of these proteins were over-expressed in the hyperplasia while 26 of them were over-expressed in the adenoma. CONCLUSION: Most proteins found to be over-expressed in the hyperplasia samples were mitochondrial, underlying the importance of the mitochondrial activity as a potential biomarker for differentiation of parathyroid hyperplasia from adenoma.

Association of rs62063857 variant of the saitohin gene with Parkinson's disease.

Saitohin gene found within the tau gene is thought to play a role in the pathogenesis of neurodegenerative diseases. The rs62063857 polymorphism originally found in the saitohin gene seems to be the responsible SNP in this event. This polymorphism is studied mostly in patients with Alzheimer's disease. Data on Parkinson's disease are scarce. Therefore, we examined the rs62063857 polymorphism in 583 Parkinson's disease patients (347 male and 236 female) and 396 healthy controls (238 male and 158 female) by a polymerase chain reaction and restriction fragment length polymorphism method to see whether it was associated with Parkinson's disease from the City of Istanbul, Turkey. The G allele frequency was 22 % in overall controls and 16 % in Parkinson's disease patients. In this study, the saitohin rs62063857 polymorphism was associated with Parkinson's disease (χ2 = 16.765; P = 0.000). Individuals with the AA genotype showed 1.7-fold increased risk for Parkinson's disease (χ2 = 16.680; P = 0.000), whereas individuals with the AG genotype revealed protection against Parkinson's disease (χ2 = 14.554; P = 0.000). After the stratification analysis according to gender, both male and female PD patients showed association with the alleles and genotypes of the rs62063857 polymorphism of the saitohin gene (χ2 = 9.476, P = 0.009; χ2 = 7.593, P = 0.022, respectively). When the Parkinson's patients were divided into two groups with regard to onset of the disease, both groups showed association with the disease. The Parkinson's patients with disease onset below 65 years of age showed 1.8-fold increased risk for the disease. The Parkinson's patients with disease onset over 65 showed more robust association with a 2.051-fold increased risk for the disease. Consequently, the rs62063857 polymorphism of the saitohin gene is a genetic risk factor for Parkinson's disease. Hence, this polymorphism may play a role in the etiology of Parkinson's disease.

Genetic variants in the PNPLA3 gene are associated with nonalcoholic steatohepatitis.

In this study, we report the association of the rs738407, rs738409, and rs2896019 variants of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) (adiponutrin) gene with nonalcoholic steatohepatitis (NASH) (χ(2)=14.528, p=0.001; χ(2)=18.882, p=0.000; χ(2)=7.449, p=0.024, respectively) in 80 patients with NASH and 303 healthy controls. We genotyped the subjects using three polymerase chain reaction-restriction fragment length polymorphism methods developed in our laboratory. Our findings confirm the findings of the recent case-control and genome-wide association studies carried out in different populations around the world. Thus, the three variants in PNPLA3 gene may be a genetic risk factor for NASH.