Neurodegeneration in Parkinsons disease is characterized by the accumulation of alpha-synuclein, aprotein encoded by theSNCAgene, in neurons. In addition to mutations, many polymorphisms have been identified in this gene, and one of theseis a dinucleotide microsatellite:SNCA-Rep1.The mechanisms by which specific configurations ofSNCA-Rep1 may contribute to the development of this disease have yet to be clarified. Inour study, a relationship between longSNCA-Rep1 alleles and Parkinsons was confirmed in the Russian population. Long allelic variants ofSNCA-Rep1 were shown to be associated with the hypomethylation of the CpG-sites in intron 1 of theSNCAgene. Long variants ofSNCA-Rep1 are supposed to exert their effect through the hypomethylation of atranscriptionally significant region of this gene. Hypomethylation is usually associated with increased expression, which, in turn, contributes to alpha-synuclein accumulation in neuronal cytoplasm, with the latter being the main molecular marker of Parkinsons disease. Further studies are needed to establish a relationship between our finding andSNCAgene expression.

Прогрессирующая наружная офтальмоплегия (ПНО) характеризуется прогрессирующим билатеральным птозом и нарушением подвижности глазных яблок в горизонтальном и вертикальном направлениях и представляет собой характерный симптом многих митохондриальных заболеваний, а не отдельную нозологическую форму. ПНО часто возникает совместно с другими системными проявлениями митохондриальной дисфункции. Правильная и ранняя диагностика ПНО первостепенна для оптимального ведения данных пациентов. В статье представлен обзор последних данных по этиологии, спектру клинических проявлений, дифференциальному диагнозу, методам диагностики и лечебным опциям для изолированной хронической ПНО и других ПНО-ассоциированных митохондриальных синдромов. К л ю ч е в ы е с л о в а: прогрессирующая наружная офтальмоплегия; митохондриальное заболевание; синдром Кернса-Сейра; офтальмоплегия; миопатия.

In recent years, epigenetic mechanisms have been implicated in the development of multifactorial diseases including neurodegenerative disorders. In Parkinson’s disease (PD), as a synucleinopathy, most studies focused on DNA methylation of SNCA gene coding alpha-synuclein but obtained results were rather contradictory. In another neurodegenerative synucleinopathy, multiple system atrophy (MSA), very few studies investigated the epigenetic regulation. This study included patients with PD (n = 82), patients with MSA (n = 24), and a control group (n = 50). In three groups, methylation levels of CpG and non-CpG sites in regulatory regions of the SNCA gene were analyzed. We revealed hypomethylation of CpG sites in the SNCA intron 1 in PD and hypermethylation of predominantly non-CpG sites in the SNCA promoter region in MSA. In PD patients, hypomethylation in the intron 1 was associated with earlier age at the disease onset. In MSA patients, hypermethylation in the promotor was associated with shorter disease duration (before examination). These results showed different patterns of the epigenetic regulation in two synucleinopathies—PD and MSA.

Neurodegeneration in Parkinsons disease is characterized by the accumulation of alpha-synuclein, aprotein encoded by theSNCAgene, in neurons. In addition to mutations, many polymorphisms have been identified in this gene, and one of theseis a dinucleotide microsatellite:SNCA-Rep1.The mechanisms by which specific configurations ofSNCA-Rep1 may contribute to the development of this disease have yet to be clarified. Inour study, a relationship between longSNCA-Rep1 alleles and Parkinsons was confirmed in the Russian population. Long allelic variants ofSNCA-Rep1 were shown to be associated with the hypomethylation of the CpG-sites in intron 1 of theSNCAgene. Long variants ofSNCA-Rep1 are supposed to exert their effect through the hypomethylation of atranscriptionally significant region of this gene. Hypomethylation is usually associated with increased expression, which, in turn, contributes to alpha-synuclein accumulation in neuronal cytoplasm, with the latter being the main molecular marker of Parkinsons disease. Further studies are needed to establish a relationship between our finding andSNCAgene expression.

Both non-epileptic sleep disturbances and epilepsy are common in patients with mucopolysaccharidoses (MPS), so diagnosis of sleep-related hypermotor epilepsy in these patients is a tackling issue. We present a case of an adult patient with MPS IIIB (Sanfilippo syndrome), who presented with numerous nocturnal events of sudden awakening and hypermotor behavior, which had been previously regarded as parasomnias. Overnight video-EEG captured numerous stereotypical seizures with ictal pattern in the frontal regions, which led the diagnosis of SHE. The patient was started with carbamazepine, which resulted in a substantial reduction in the number of seizures. Our report provides further support for use of overnight video-EEG in the differential diagnosis of sleeprelated disorders in MPS, yet true incidence of SHE in MPS patients remains unknown.