What does this mean for patients? Familial Mediterranean fever (FMF) is an inherited autoinflammatory disorder that causes recurrent fever and pain in the joints, chest and abdomen. However, it is not just a rheumatological disorder. FMF can also aggravate the patient’s clinical condition or trigger other underlying diseases. We described a 17-year-old male patient with FMF, diabetes and dystonia (uncontrolled muscle movements). Dystonia is associated with variations in the VPS16 gene, while FMF is associated with variations in the MEFV gene. Due to the genetic nature of FMF and dystonia, we also described the patient’s family. We found that the patient’s sister also had FMF, diabetes and dystonia. This suggests that if a person has specific variations of both the VPS16 and MEFV genes, they may have FMF, dystonia and diabetes from a young age.

Objectives: This study aimed to investigate the methylation changes of related genes in the peripheral blood and their clinical significance in Parkinson's disease (PD) and whether the methylation change of the gene encoding long noncoding RNA was different in the blood of patients and controls. Patients and methods: This prospective cross-sectional, controlled study was conducted with 45 participants (22 males, 23 females; mean age: 60.7±5.9 years; range, 53 to 75 years) between June 2020 and June 2021. Drug-naive patients diagnosed with PD were included in this study. Those with PD and a Mini-Mental State Examination (MMSE) score >23 were defined as Group 1 (n=15), and those with PD and an MMSE score ≤23 were defined as Group 2 (n=15). Controls were included in Group 3 (n=15). The methylation changes of genes HSP70, HSP90, heat shock factor 1 (HSF1), heat shock RNA 1 (HSR1), and eukaryotic translation elongation factor 1 alpha (eEF1α) were investigated with methylation-specific real-time quantitative polymerase chain reaction analysis. Results: The eEF1α was significantly more hypermethylated in Group 1. In Group 2, HSP70, HSP90 HSF1, HSR1, and eEF1α were significantly hypomethylated compared to Group 1 and Group 3 (for all genes p<0.001). The HSF1 hypomethylation was negatively correlated with MMSE and positively correlated with depression scores (p=0.03 and p=0.013, respectively). The correlation of eEF1α with MMSE and depression was the opposite of HSF1 (p<0.001 and p=0.013, respectively). Conclusion: Cell line and autopsy studies indicate that eEF1α hypermethylation might be one of the main molecules triggering alpha-synuclein aggregation in the pathogenesis of PD. Therefore, eEF1α may be a molecule that can be used as a peripheral biomarker. The findings supported this idea as it was more hypermethylated in PD patients than in controls, whereas its negative regulator HSF1 was hypomethylated and correlated with the clinic. Furthermore, the worsening of cognitive functions and depression in PD patients may affect methylation levels of chaperone genes in the peripheral blood.

Purpose: To evaluate structural, microvascular, and functional neuro-ophthalmologic changes in severe obstructive sleep apnea syndrome (OSAS) and to investigate the effects of 6-month continuous positive airway pressure (CPAP) therapy using a multimodal approach. Methods: In this prospective case–control study, 38 patients with PSG-confirmed severe OSAS and 19 controls were enrolled. All participants underwent optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), and visual field (VF) testing (24–2 and 10–2). Thirty patients with adequate CPAP adherence were reassessed after 6 months. Baseline comparisons were additionally adjusted for body mass index (BMI), and false discovery rate (FDR) correction was applied for multiple comparisons. Results: Baseline neuro-ophthalmologic differences between OSAS patients and controls did not remain statistically significant after BMI adjustment and FDR correction. Following CPAP therapy, significant increases in average and inferior peripapillary retinal nerve fiber layer (RNFL) thickness were observed and remained significant after FDR correction. Significant improvements were also detected in 24–2 VF indices (VFI, MD, and PSD) and 10–2 PSD values after treatment. In contrast, OCTA-derived vascular parameters and macular thickness changes did not remain significant after correction for multiple comparisons. All polysomnographic parameters and Epworth Sleepiness Scale scores improved significantly after treatment. Conclusions: Although baseline cross-sectional neuro-ophthalmologic differences were attenuated after BMI adjustment and multiple-comparison correction, longitudinal analyses demonstrated significant structural and functional improvement following CPAP therapy in severe OSAS. Multimodal assessment combining OCT and retinal and macular perimetry may provide a useful framework for monitoring treatment-related neuro-ophthalmologic changes in OSAS.