Non-related Controls Research Articles (Page 1)

Secreted clusterin inhibits keloid formation by promoting fibroblast apoptosis.

Conflicting results have been reported on dietary factors in inflammatory bowel diseases (IBDs). Here, we compared the dietary intakes of IBD patients with those of paired healthy relatives (HRs), aiming to minimize the impact of genetic and environmental confounders. Patients with Crohn's disease (CD, N = 45) and ulcerative colitis (UC, N = 20), their paired HRs (NCD-HR = 45, NUC-HR = 20) and healthy non-relative (HNR, NCD-HNR = 25, NUC-HNR = 55) controls were recruited. Participants have kept dietary habits since the onset of IBDs and report no other recent digestive diseases or surgeries. Pre-illness dietary factors were assessed through 24-hour recall interviews. Statistical analyses included Analysis of Variance, Fisher's exact tests, Wilcoxon rank sum tests, logistic regressions, Area Under the Receiver-Operator Curve (AUROC) analysis, and Least Absolute Shrinkage and Selection Operator (LASSO) regression. Dietary features identified in IBD patients using the HR controls differed from those identified using the HNR controls. For CD, lower intakes of vitamin C, dietary fiber, calcium, vegetables, decanoic acid (10:0), milk, dairy foods, and β-carotene were identified as risk factors when compared to HRs. LASSO regression highlighted milk, vegetables, and vitamin C as the most significant risk factors for CD. In UC patients, lower intakes of phosphorus, docosapentaenoic acid (DPA, 22:5, n-3), vitamins B-2 and B-12, and choline, along with a higher intake of α-carotene, were identified as risk factors compared to HRs. LASSO regression emphasized DPA, vitamins B-2 and B-12, and α-carotene as the most significant risk factors for UC. Monitoring dietary intake patterns is crucial for the prevention and personalized treatment of CD and UC.

Whole genome sequencing (WGS) marks a turning point for outbreak investigations for microorganisms related to public health matters, like Legionella pneumophila (Lp). Here, we evaluated the available Lp WGS typing tools for isolates of previously documented Belgian outbreaks, as well as small groups of related and non-related isolates. One reference strain and 77 clinical and environmental isolates were evaluated. Seven isolates belong to a Sequence Type (ST) 36 outbreak in 1999 and sixteen (ten clinical, two matching environmental and four non-related controls) belong to another ST1 outbreak in 1985–1987. The remaining isolates belong to small groups of related and non-related isolates of diverse ST’s. WGS was performed and data were analysed using whole genome (wg) and core genome (cg) multilocus sequence typing (MLST) with “Ridom SeqSphere + ” (cgMLST), “Applied Maths-Bionumerics” (wgMLST) and the 50 loci cgMLST (CDC/ESGLI_ESCMID). Results of the three tools were concordant with the traditional Sequence Based Typing (SBT). The known outbreaks and small clusters could be detected and clear discrimination of ST1 non-related isolates was obtained. In addition, the 50 loci cgMLST allowed to classify the isolates into subtypes because almost all the 50 genes could be called in all the analysed isolates, which was not achieved by the other tools. This is a big advantage in terms of standardisation and comparison between laboratories for future epidemiological investigations. WGS allowed to analyse a large volume of samples and generated more accurate conclusions for outbreak investigations compared to other typing methods due to its higher discriminatory power and throughput.

BackgroundPeutz–Jeghers syndrome (PJS), a rare dominantly inherited disease, is primarily characterized by hamartomatous polyps and melanotic macules as well as by an increased risk of cancer. The current study aimed to identify the pathogenic gene and pathogenic mechanism of a proband with PJS, thereby offering precise prevention and treatment strategies for PJS.MethodsA detailed clinical examination was performed of the proband diagnosed with PJS and her family members. In addition, peripheral venous blood was collected from the family members to extract genomic DNA. The pathogenic genes of the proband were identified using whole-exome sequencing, and the candidate pathogenic variants were verified via Sanger sequencing. Meanwhile, co-segregation tests were performed among six family members. Finally, reverse transcription-polymerase chain reaction (RT-PCR) was performed to assess transcript variants in the peripheral blood cells of patients and non-related healthy controls.ResultsGenetic testing revealed a rare splicing variant c.921-1G > C in STK11 in the proband and in her sister and nephew, and the variant co-segregated among the affected family members and nonrelated healthy controls. The proband phenotypically presented with a rare gastric-type adenocarcinoma of the cervix. RT-PCR revealed that the STK11 c.921-1G > C variant could produce two transcripts. Of note, 40 base pairs were deleted in the aberrant transcript between exons 3 and 4, resulting in a frameshift variant and premature termination of the amino acid in exon 6 and ultimately leading to the loss of its functional domain in the STK11 protein. Finally, RT-PCR showed that compared with healthy controls, STK11 mRNA expression level was < 50% in patients.ConclusionThe present study results indicated that the rare splicing variant c.921-1G > C in intron 7 of STK11 may be a pathogenic variant in patients with PJS. However, this variant (in intron 7) may not produce abnormal transcripts (deletion of 40 base pairs between exons 3 and 4), and PJS may be attributed to the decrease in STK11 expression. Therefore, this study emphasized the importance of genetic counseling, pre-symptomatic monitoring, and early complication management in PJS.

Chinese carrier of the HNF1A p.Gln444fs variant exhibits enhanced response to sulfonylureas

Previous research has shown a significant link between gut microbiota in children with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). However, much remains unknown because of the heterogeneity of disorders and the potential confounders such as dietary patterns and control group variations. Children aged 6-12 years who had been clinically diagnosed with ASD and/or ADHD, their unaffected neurotypical siblings, and non-related neurotypical volunteers were recruited cross-sectionally. The ASD diagnosis was confirmed using the Autism Diagnostic Observation Schedule-2 (ADOS-2) in all patients, including those with ADHD. Standardized DNA extraction and sequencing methods were used to compare gut microbial alpha-diversity among the groups. Dietary diversity was calculated from a standardized dietary questionnaire form. We compared the difference in gut microbiome between patients with ASD and/or ADHD with neurotypical siblings and non-related neurotypical controls. Ninety-eight subjects were included in the study (18 with ASD, 19 with ADHD, 20 with both ASD and ADHD, 13 neurotypical siblings, and 28 non-related neurotypical controls). The alpha-diversity indices, such as Chao 1 and Shannon index, showed a significant difference between the groups in a Linear mixed-effect model (F(4, 93) = 4.539, p = .02), (F(4, 93) = 3.185, p = .017), respectively. In a post-hoc pairwise comparison, patients with ASD had lower alpha-diversity compared with non-related controls after Bonferroni correction. Dietary diversity shown in Shannon index did not differ among the groups (F(4, 84) = 1.494, p = .211). Our study indicates disorder-specific microbiome differences in patients with ASD. In future research on gut microbiota in neurodevelopmental disorders, it is necessary to consider the impact of ASD and ADHD co-occurrence, and strictly control for background information such as diet, to elucidate the gut-microbiota interaction in ASD and ADHD for exploring the potential of therapeutic interventions.

ABSTRACT An association has been suggested between altered gut microbiota, and attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), respectively. Thus, we analyzed the gut microbiota composition in children and adolescents with or without these disorders and evaluated the systemic effects of these bacteria. We recruited study participants diagnosed with ADHD, ASD, and comorbid ADHD/ASD, while the control groups consisted both of siblings and non-related children. The gut microbiota was analyzed by 16S rRNA gene sequencing of the V4 region, while the concentration of lipopolysaccharide-binding protein (LBP), cytokines, and other signaling molecules were measured in plasma. Importantly the gut microbiota compositions of cases with ADHD and ASD were highly similar for both alpha- and beta-diversity while differing from that of non-related controls. Furthermore, a subset of ADHD and ASD cases had an increased LBP concentration compared to non-affected children, which was positively correlated with interleukin (IL)-8, 12, and 13. These observations indicate disruption of the intestinal barrier and immune dysregulation among the subset of children with ADHD or ASD.

The ongoing COVID-19 pandemic continues to pose a need for new and efficient therapeutic strategies. We explored antisense therapy using oligonucleotides targeting the severe acute respiratory syndrome coronavirus (SARS-CoV-2) genome. We predicted in silico four antisense oligonucleotides (ASO gapmers with 100% PTO linkages and LNA modifications at their 5' and 3'ends) targeting viral regions ORF1a, ORF1b, N and the 5'UTR of the SARS-CoV-2 genome. Efficiency of ASOs was tested by transfection in human ACE2-expressing HEK-293T cells and monkey VeroE6/TMPRSS2 cells infected with SARS-CoV-2. The ORF1b-targeting ASO was the most efficient, with a 71% reduction in the number of viral genome copies. N- and 5'UTR-targeting ASOs also significantly reduced viral replication by 55 and 63%, respectively, compared to non-related control ASO (ASO-C). Viral titration revealed a significant decrease in SARS-CoV-2 multiplication both in culture media and in cells. These results show that anti-ORF1b ASO can specifically reduce SARS-CoV-2 genome replication in vitro in two different cell infection models. The present study presents proof-of concept of antisense oligonucleotide technology as a promising therapeutic strategy for COVID-19.

Maturity-onset diabetes of the young (MODY) is rare monogenic diabetes. However, MODY is often undiagnosed or misdiagnosed. In this study, we aimed to investigate the pathogenic gene for diabetes and provide precise treatment for diabetes patients in three families. Three families with suspected MODY were enrolled and screened for germline mutations using Whole exome sequencing (WES). Candidate pathogenic variants were validated in other family members and non-related healthy controls. Three heterozygous missense mutations in the ABCC8 gene (NM_001287174), c.1555 C>T (p.R519C), c.3706 A>G (p.I1236V), and c.2885 C>T (p.S962L) were found in families A, B, and C, respectively. All mutation sites cosegregated with diabetes, were predicted to be harmful by bioinformatics and were not found in non-related healthy controls. Two probands (onset ages, 8 and 12 years) were sensitive to glimepiride. However, an insufficient dose (2 mg/day) led to ketoacidosis. When the dosage of glimepiride was increased to 4 mg/day, blood sugar remained under control. A dose of 4 mg glimepiride daily also effectively controlled blood sugar in an adult patient 25-year-old. In addition, all patients were sensitive to liraglutide, which could control blood sugar better. These data suggest that ABCC8 was the pathogenic gene in three families with diabetes. Glimepiride (2 mg/day) was not effective in controlling blood sugar in children with ABCC8 mutations, however, 4 mg/daily glimepiride was effective in both adults and children. Moreover, liraglutide was effective in controlling blood sugar in both adults and children with ABCC8 mutations.

IgA nephropathy (IgAN) is a leading cause of kidney failure, yet little is known about the immunopathogenesis of this disease. IgAN is characterized by deposition of IgA in the kidney glomeruli, but the source and stimulus for IgA production are not known. Clinical and experimental data suggest a role for aberrant immune responses to mucosal microbiota in IgAN, and in some countries with high disease prevalence, tonsillectomy is regarded as standard-of-care therapy. To evaluate the relationship between microbiota and mucosal immune responses, we characterized the tonsil microbiota in patients with IgAN versus nonrelated household-matched control group participants and identified increased carriage of the genus Neisseria and elevated Neisseria-targeted serum IgA in IgAN patients. We reverse-translated these findings in experimental IgAN driven by BAFF overexpression in BAFF-transgenic mice rendered susceptible to Neisseria infection by introduction of a humanized CEACAM-1 transgene (B × hC-Tg). Colonization of B × hC-Tg mice with Neisseria yielded augmented levels of systemic Neisseria-specific IgA. Using a custom ELISPOT assay, we discovered anti-Neisseria–specific IgA-secreting cells within the kidneys of these mice. These findings suggest a role for cytokine-driven aberrant mucosal immune responses to oropharyngeal pathobionts, such as Neisseria, in the immunopathogenesis of IgAN. Furthermore, in the presence of excess BAFF, pathobiont-specific IgA can be produced in situ within the kidney.

Objective:Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder whose cause remains unknown. Oxidative stress is one of the possible causes of many disorders, including neurological ones. This study aims to measure some oxidative stress biomarkers (Malondialdehyde “MDA,” Advanced Oxidation Protein Product “AOPP,” Glutathione “GSH”) within Syrian children with ASD.Methods:MDA, AOPP & GSH were measured in the plasma of a total of 60 children. The ages of the children ranged from 1 to 13 years old. Thirty children had ASD and were compared with 30 controls that don’t have ASD. Fifteen of the controls were siblings of an ASD child, while the remaining 15 had no relations with ASD.Results:MDA and AOPP plasma levels were higher in ASD children compared with non-related controls (P = .0001). However, there were no significant differences between MDA and AOPP plasma levels in ASD children in comparison with related controls (P > .05). Alternatively, GSH plasma levels were lower in ASD children compared with both related and non-related controls (P = .0001).Conclusion:Further studies are needed to investigate more regarding the diagnostic use of oxidative stress biomarkers, and the therapeutic use of antioxidants in children affected with the autism spectrum disorder.

ObjectiveTo determine the pathogenic gene and explore the clinical characteristics of maturity-onset diabetes of the young type 2 (MODY2) pedigree caused by a mutation in the glucokinase (GCK) gene.MethodsUsing whole-exome sequencing (WES), the pathogenic gene was detected in the proband—a 20-year-old young man who was accidentally found with hyperglycemia, no ketosis tendency, and a family history of diabetes. The family members of the proband were examined. In addition, relevant clinical data were obtained and genomic DNA from peripheral blood was obtained. Pathologic variants of the candidate were verified by Sanger sequencing technology, and cosegregation tests were conducted among other family members and non-related healthy controls. After adjusting the treatment plan based on the results of genetic testing, changes in biochemical parameters, such as blood glucose levels and HAblc levels were determined.ResultsIn the GCK gene (NM_000162) in exon 9, a heterozygous missense mutation c.1160C > T (p.Ala387Val) was found in the proband, his father, uncle, and grandmother. Thus mutation, which was found to co-segregate with diabetes, was the first discovery of such a mutation in the Asian population. After stopping hypoglycemic drug treatment, good glycemic control was achieved with diet and exercise therapy.ConclusionGCK gene mutation c.1160C > T (p.Ala387Val) is the pathogenic gene in the GCK-MODY pedigree. Formulating an optimized and personalized treatment strategy can reduce unnecessary excessive medical treatment and adverse drug reactions, and maintain a good HbA1c compliance rate

ABSTRACTMicrobiome sequence data have been used to characterize Crohn's disease (CD) and ulcerative colitis (UC). Based on these data, we have previously identified microbiomarkers at the genus level to predict CD and CD relapse. However, microbial load was underexplored as a potential biomarker in inflammatory bowel disease (IBD). Here, we sought to study the use of fungal and bacterial loads as biomarkers to detect both CD and UC and CD and UC relapse. We analyzed the fecal fungal and bacterial loads of 294 stool samples obtained from 206 participants using real-time PCR amplification of the ITS2 region and the 16S rRNA gene, respectively. We combined the microbial data with demographic and standard laboratory data to diagnose ileal or ileocolonic CD and UC and predict disease relapse using the random forest algorithm. Fungal and bacterial loads were significantly different between healthy relatives of IBD patients and nonrelated healthy controls, between CD and UC patients in endoscopic remission, and between UC patients in relapse and non-UC individuals. Microbial load data combined with demographic and standard laboratory data improved the performance of the random forest models by 18%, reaching an average area under the receiver operating characteristic curve (AUC) of 0.842 (95% confidence interval [CI], 0.65 to 0.98), for IBD diagnosis and enhanced CD and UC discrimination and CD and UC relapse prediction. Our findings show that fecal fungal and bacterial loads could provide physicians with a noninvasive tool to discriminate disease subtypes or to predict disease flare in the clinical setting.IMPORTANCE Next-generation sequence data analysis has allowed a better understanding of the pathophysiology of IBD, relating microbiome composition and functions to the disease. Microbiome composition profiling may provide efficient diagnosis and prognosis tools in IBD. However, the bacterial and fungal loads of the fecal microbiota are underexplored as potential biomarkers of IBD. Ulcerative colitis (UC) patients have higher fecal fungal and bacterial loads than patients with ileal or ileocolonic CD. CD patients who relapsed harbor more-unstable fungal and bacterial loads than those of relapsed UC patients. Fecal fungal and bacterial load data improved prediction performance by 18% for IBD diagnosis based solely on clinical data and enhanced CD and UC discrimination and prediction of CD and UC relapse. Combined with existing laboratory biomarkers such as fecal calprotectin and C-reactive protein (CRP), microbial loads may improve the diagnostic accuracy of IBD and of ileal CD and UC disease activity and prediction of UC and ileal CD clinical relapse.

Study ObjectivesNarcolepsy type 1 (NT1) is associated with hypocretin neuron loss. However, there are still unexplained phenotypic NT1 features. We investigated the associations between clinical and sleep phenotypic characteristics, the NT1-associated P2RY11 polymorphism rs2305795, and P2Y11 protein levels in T lymphocytes in patients with NT1, their first-degree relatives and unrelated controls.MethodsThe P2RY11 SNP was genotyped in 100 patients (90/100 H1N1-(Pandemrix)-vaccinated), 119 related and 123 non-related controls. CD4 and CD8 T lymphocyte P2Y11 protein levels were quantified using flow cytometry in 167 patients and relatives. Symptoms and sleep recording parameters were also collected.ResultsWe found an association between NT1 and the rs2305795 A allele (OR = 2, 95% CI (1.3, 3.0), p = 0.001). T lymphocyte P2Y11 protein levels were significantly lower in patients and relatives homozygous for the rs2305795 risk A allele (CD4: p = 0.012; CD8: p = 0.007). The nocturnal sleep fragmentation index was significantly negatively correlated with patients’ P2Y11 protein levels (CD4: p = 0.004; CD8: p = 0.006). Mean MSLT sleep latency, REM-sleep latency, and core clinical symptoms were not associated with P2Y11 protein levels.ConclusionsWe confirmed that the P2RY11 polymorphism rs2305795 is associated with NT1 also in a mainly H1N1-(Pandemrix)-vaccinated cohort. We demonstrated that homozygosity for the A risk allele is associated with lower P2Y11 protein levels. A high level of nocturnal sleep fragmentation was associated with low P2Y11 levels in patients. This suggests that P2Y11 has a previously unknown function in sleep-wake stabilization that affects the severity of NT1.

Oral cancer due to betel quid chewing habit is very common in South Asian countries. We attempted to detect the presence of a novel gene in epithelial cells stimulated with arecoline, a main component of betel quid. Human gingival epithelial progenitors were cultured and treated with a 3-day alternating regimen with/without 50μg/ml arecoline for 1month. DNA microarray and methylation arrays were analyzed to identify the candidate genes. Immunohistochemical staining was performed in the tissue samples. Genome-wide analyses, quantitative reverse transcription PCR and quantitative methylation-specific PCR revealed DUSP4 as the most significant and promising gene. The methylation levels of DUSP4 were significantly higher in the betel quid-related oral squamous cell carcinoma (OSCC) than those in the non-related OSCC and controls (Mann-Whitney U test, p < 0.05). The number of DUSP4 immunopositive cells in betel quid-related OSCC was significantly higher than those from the non-chewing patients and the controls (p < 0.05). Hypermethylation of DUSP4 may be considered as a specific event in betel quid-related oral cancer.

Multiple sclerosis (MS), a disease of the central nervous system (CNS), is associated with damage to the myelin sheath of neurons. It is demonstrated that vitamin D deficiency plays an important role in the development of the disease. Binding of vitamin D to its specific nuclear receptors is a way to exert its function. Possible correlation between the vitamin D receptor (VDR) gene and MS was evaluated in the Azeri population of Iran. Different genotypes of the Bsml site were determined by using the PCR-RFLP method in 148 MS patients and 220 non-relative healthy controls. In MS patients, genotype bb was significantly higher than the healthy controls (p<0.05). Additionally, most subjects of the MS group had been insufficiently exposed to sunlight before the age of 15 (p<0.001). Our findings indicated that the red meat intake in MS patients was significantly higher than the healthy controls (p<0.001). In addition, the healthy controls had appropriate dieting behaviors in comparison to MS patients (excessive intake of some foods) (p=0.0001). In conclusion, genotype BB and sufficient exposure to sunlight before the age of 15 were the protective factors against MS. Although, excessive consumption of red meat and inappropriate dieting behaviors were predisposing factors to MS disease.

Cytokines as important mediators have a critical role in appropriate immune responses, the irregular production of which can lead to Multiple Sclerosis (MS). Proinflammatory cytokine interleukin-1 (IL-1) triggers inflammatory responses. Function and production of the cytokine are influenced by IL-1 coding gene polymorphism and those antagonists gene polymorphism. The aim of the present study was to evaluate the possible correlation between MS and IL-1 related alleles in Azeri population of Iran. Variable number tandem repeats (VNTR) genotypes of 150 MS patients and 220 healthy non-relative controls were determined. In the healthy controls, genotype TT at IL-1A (-889) location was significantly higher than the MS patients (p=0.0001). However, a significant difference was not found between the two groups in genotypic/allelic frequency at IL- 1B+ 3953 location. Evaluation of the IL-1RA gene revealed that genotype 1/2, and genotype 1/3 were significantly higher in the healthy controls and MS patients, respectively. Our findings indicated that the consumption of fast-food in MS patients was significantly higher than controls (p= <0.05). Also, a considerable number of MS patients had inappropriate dieting behaviors such as not eating breakfast (p= 0.0001), and irregular eating habits (p= 0.0001). Polymorphisms of the IL-1B genes and common alleles of IL-1RA were not considered as risk factors for MS disease. However, genotype TT at IL-1A (-889) location and the rare allele of IL-1RA3 can be a potential risk factor for the disease. Furthermore, inappropriate dieting behaviors and consumption of fast-food can increase the risk of MS.

There could be an overlap of monogenic diabetes and early-onset type 2 diabetes mellitus. Precise diagnosis of early-onset diabetes has proven valuable for understanding the mechanism of diabetes and selecting optimal therapy. The majority of maturity onset diabetes of the young (MODY) pathogenic genes in China is still unknown. In this study, a family with suspected MODY was enrolled. Whole-exome sequencing (WES) was used to analyze the variants of the proband. Variants were filtered according to their frequency, location, functional consequences, and bioinformatics software. Candidate pathogenic variants were validated by Sanger sequencing and tested for cosegregation in other members of the family and nonrelated healthy controls. KEGG (Kyoto Encyclopedia of Genes and Genomes) and PPI (protein-protein interaction) analysis were conducted using the DAVID (Database for Annotation, Visualization, and Integrated Discovery) and the STRING online analysis tools for the candidate pathogenic gene. A total of 123291 variants including 105344 SNPs and 17947 InDels were found in WES. A likely pathogenic rare missense heterozygous mutation in diabetes genes (c.2137C > T, p.His713Tyr in IRS1) was identified, which was a cosegregate in this family and not in nonrelated healthy controls. The position of the mutation in the aminoacid sequence of the gene is highly conserved among the species. 2 significantly enriched KEGG pathways were identified including bta04930, type II diabetes mellitus (GCK, INS, PDX1, ABCC8, and IRS1), and bta04910, insulin signaling pathway (GCK, INS, and IRS1). PPI analysis displayed that IRS1 interacts with 3 known pathogenic proteins including INS, KCNJ11, and GCK. We conclude that WES could be an initial option for genetic testing in patients with early-onset diabetes. IRS1 p.His713Tyr is implicated as a possible pathogenic mutation in monogenic diabetes, which might require further validation, and the precise molecular mechanism underlying the influence of IRS1 p.His713Tyr on the development of diabetes remains to be determined in the further prospective studies.

Frataxin deficiency, responsible for Friedreich's ataxia (FRDA), is crucial for cell survival since it critically affects viability of neurons, pancreatic beta cells and cardiomyocytes. In FRDA, the heart is frequently affected with typical manifestation of hypertrophic cardiomyopathy, which can progress to heart failure and cause premature death. A microarray analysis performed on FRDA patient's lymphoblastoid cells stably reconstituted with frataxin, indicated HS-1-associated protein X-1 (HAX-1) as the most significantly upregulated transcript (FC = +2, P < 0.0006). quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and western blot analysis performed on (I) HEK293 stably transfected with empty vector compared to wild-type frataxin and (II) lymphoblasts from FRDA patients show that low frataxin mRNA and protein expression correspond to reduced levels of HAX-1. Frataxin overexpression and silencing were also performed in the AC16 human cardiomyocyte cell line. HAX-1 protein levels are indeed regulated through frataxin modulation. Moreover, correlation between frataxin and HAX-1 was further evaluated in peripheral blood mononuclear cells (PBMCs) from FRDA patients and from non-related healthy controls. A regression model for frataxin which included HAX-1, group membership and group* HAX-1 interaction revealed that frataxin and HAX-1 are associated both at mRNA and protein levels. Additionally, a linked expression of FXN, HAX-1 and antioxidant defence proteins MnSOD and Nrf2 was observed both in PBMCs and AC16 cardiomyocytes. Our results suggest that HAX-1 could be considered as a potential biomarker of cardiac disease in FRDA and the evaluation of its expression might provide insights into its pathogenesis as well as improving risk stratification strategies.

Background : although the exact pathogenesis of auditory hallucinations is not yet known, some suggested the impairment of perception and processing of auditory information as a possible explanation. So, the aim of this study is to evaluate auditory pathways of schizophrenic patients using auditory brainstem responses (ABR). Methods : schizophrenic patients with auditory hallucinations and age and sex matched healthy non-relative controls were recruited in this case-control study. Scale for assessment of positive symptoms (SAPS) was used for rating the severity of hallucinations. Then, ABR recorded from all participants and the latencies of waves I, II, III, IV, V and inter-peak latencies (IPL) of waves I-III, III-V were analyzed on both sides. Chi squire and independent t tests were applied for statistical analysis. P-value≤0.05 was considered significant. Results : 39 patients and 35 controls were included. Latencies of waves III and V and IPL of III-V were significantly prolonged on the left side. Disease duration had no influence on the results. Conclusion : there is a link between abnormal ABRs and auditory hallucinations in schizophrenic patients that indicates dysfunction and abnormal asymmetry of auditory pathways in these patients.