Testing Genes Implicated in the Novel Case of Familial Hemiplegic Migraine

© 2016, Springer Science+Business Media New York.Familial hemiplegic migraine (FHM) is a rare monogenetic form of migraine associated with aura and motor dysfunctions. Molecular mechanisms of FHM still remain unknown; however, genetic predisposition to the disease has been suggested. We report several cases of FHM diagnosed in three generations of ethnic Tatars, Russian Federation. Apart from clear family character, patients presented with typical features of FHM including aura and ataxia. In order to determine disease genetic markers in these cases, we sequenced several genes (CACNA1A, ATP1A2, and SCN1A) previously reported in FHM. Sequence analysis demonstrated absence of the previously identified mutations in genes studied. This is the first genetic study of FHM in the Tatar population. The lack of known FHM associated mutation in these patients suggests presence of yet unidentified mutations in some other genes. Further studies including full genome sequencing are needed to clarify the genetic background of FHM cases in the Tatar population

Genetic Diversity of Puumala Virus Isolates in the Republic of Tatarstan and the Republic of Mordovia

© 2016, Springer Science+Business Media New York.Puumala virus (PUUV) is the main causative agent of nephropathia epidemica (NE), a mild form of the hemorrhagic fever with renal syndrome (HFRS). The bank vole (Myodes glareolus) is the natural reservoir of PUUV. Several distinct lineages of PUUV have been identified that circulate in bank voles worldwide; however, little is known about genetic diversity of the PUUV strains that cause NE in the Volga Region of Russia. Partial PUUV S segment sequences (171 bp) were isolated from 25 NE serum samples collected in the Republic of Tatarstan (RT) and eight samples from the Republic of Mordovia (MR). Phylogenetic analysis revealed that 14 PUUV sequences from RT were clustered together with the strains previously identified circulating in Russia, including those from Samara Oblast, RT (Kazan) and the Republic of Udmurtia. Interestingly, 11 PUUV sequences were grouped together with the virus strain from Pieksamaki, which belongs to the PUUV genetic lineage circulating in Finland. The majority of PUUV sequences isolated from MR were clustered with the strains from RT (Kazan) and Udmurtia; however, few strains were genetically closer to the strains “Ufa97.11” or the Pieksamaki. Thus, PUUV associated with NE in RT and MR displays high genetic diversity, suggesting co-circulation of at least two distinct genetic lineages in the Volga Region of Russia

Case of meningitis in a neonate caused by an extended-spectrum-beta-lactamase-producing strain of hypervirulent Klebsiella pneumoniae

© 2017 Khaertynov, Anokhin, Davidyuk, Nicolaeva, Khalioullina, Semyenova, Alatyrev, Skvortsova and Abrahamyan. Klebsiella pneumoniae is one of the most important infectious agents among neonates. This pathogen has a potential to develop an increased antimicrobial resistance and virulence. The classic non-virulent strain of K. pneumoniae, producing an extended-spectrum beta-lactamases (ESBL), is associated with nosocomial infection mainly in preterm neonates. Hypervirulent K. pneumoniae strains are associated with invasive infection among previously healthy ambulatory patients, and most of them exhibit antimicrobial susceptibility. During the last few years, several cases of diseases caused by hypervirulent K. pneumoniae producing ESBL have been registered in different geographical regions of the world. However , reports of such cases in neonates are rare. Here, we reported that this pathogen can cause pyogenic meningitis in full-term neonate with poor prognosis. A previously healthy, full-term, 12-day-old neonate was admitted to the infectious diseases hospital with suspected meningitis. The clinical symptoms included loss of appetite, irritability, fever, seizures, and a bulging anterior fontanelle. The analysis of the cerebrospinal fluid confirmed the diagnosis of meningitis. Blood and cerebrospinal fluid cultures were positive for K. pneumoniae, producing ESBL. K. pneumoniae isolates were resistant to aminopenicillins, 3rd generation cephalosporins but were sensitive to imipenem and meropenem. The "string test" was positive. The study of the virulence factors of K. pneumoniae by PCR revealed the presence of the rmpA gene. A combination of K. pneumoniae virulence and drug resistance complicated by cerebral oedema led to the death of the neonate. We concluded that both the risk of developing severe forms of infection and the outcome of the disease due to K. pneumonia are associated with the phenotypic features of the pathogen such as its antibiotic susceptibility and virulence factors. Emergence of the ESBL-producing strain of hypervirulent K. pneumoniae could represent a new serious threat to public health, suggesting an urgent need to enhance clinical awareness and epidemiological surveillance

High Triglycerides Are Associated with Low Thrombocyte Counts and High VEGF in Nephropathia Epidemica

© 2016 Ekaterina V. Martynova et al.Nephropathia epidemica (NE) is a mild form of hemorrhagic fever with renal syndrome. Several reports have demonstrated a severe alteration in lipoprotein metabolism. However, little is known about changes in circulating lipids in NE. The objectives of this study were to evaluate changes in serum total cholesterol, high density cholesterol (HDCL), and triglycerides. In addition to evaluation of serum cytokine activation associations, changes in lipid profile and cytokine activation were determined for gender, thrombocyte counts, and VEGF. Elevated levels of triglycerides and decreased HDCL were observed in NE, while total cholesterol did not differ from controls. High triglycerides were associated with both the lowest thrombocyte counts and high serum VEGF, as well as a high severity score. Additionally, there were higher levels of triglycerides in male than female NE patients. Low triglycerides were associated with upregulation of IFN-γ and IL-12, suggesting activation of Th1 helper cells. Furthermore, levels of IFN-γ and IL-12 were increased in patients with lower severity scores, suggesting that a Th1 type immune response is playing protective role in NE. These combined data advance the understanding of NE pathogenesis and indicate a role for high triglycerides in disease severity

Serum cytokine signature that discriminates Helicobacter pylori positive and negative juvenile gastroduodenitis

© 2016 Khaiboullina, Abdulkhakov, Khalikova, Safina, Martynova, Davidyuk, Khuzin, Faizullina, Lombardi, Cherepnev and Rizvanov.Gastroduodenitis caused by H. pylori, often acquired in early childhood, is found in about 50% of the adult population. Although H. pylori infections can remain asymptomatic, its virulence factors usually trigger epithelial vacuolization and degeneration, loss of microvilli, disintegration of cytoplasm, and leukocyte accumulation. It is believed that leukocyte infiltration is driven by cytokines produced locally in infected tissue. However, so far little is known about changes in serum cytokines in juvenile patients infected with H. pylori. Serum cytokine profiles were analyzed in 62 juvenile patients diagnosed with gastroduodenitis using the Bio-Plex multiplex assay. H. pylori infection was confirmed in 32 patients, while 30 patients were H. pylori-free. Cytokines CXCL5 and CXCL6, potent neutrophil chemoattractants, were upregulated in all patients diagnosed with gastroduodenitis. Serum levels of IL8, a prototype neutrophil attractant, remained unchanged in subjects with gastroduodenitis relative to controls. Therefore, our data suggest that CXCL5 and CXCL6 play a role in directing neutrophil trafficking into inflamed gastroduodenal tissue. In addition, the CCL25/GM-CSF ratio differed significantly between H. pylori-positive and -negative juveniles. Further, study is needed to evaluate the role of CCL25 and GM-CSF in the pathogenesis of the different etiologies of gastroduodenitis

Cerebellar atrophy and changes in cytokines associated with the CACNA1A R583Q mutation in a Russian familial hemiplegic migraine type 1 family

© 2017 Khaiboullina, Mendelevich, Shigapova, Shagimardanova, Gazizova, Nikitin, Martynova, Davidyuk, Bogdanov, Gusev, van den Maagdenberg, Giniatullin and Rizvanov. Background: Immune mechanisms recently emerged as important contributors to migraine pathology with cytokines affecting neuronal excitation. Therefore, elucidating the profile of cytokines activated in various forms of migraine, including those with a known genetic cause, can help in diagnostic and therapeutic approaches. Methods: Here we (i) performed exome sequencing to identify the causal gene mutation and (ii) measured, using Bio-Plex technology, 22 cytokines in serum of patients with familial migraine (two with hemiplegic migraine and two with migraine with aura) from a Russian family that ethnically belongs to the Tatar population. MRI scanning was used to assess cerebellar atrophy associated with migraine in mutation carriers. Results: Whole-exome sequencing revealed the R583Q missense mutation in the CACNA1A gene in the two patients with hemiplegic migraine and cerebellar ataxia with atrophy, confirming a FHM1 disorder. Two further patients did not have the mutation and suffered from migraine with aura. Elevated serum levels of pro-inflammatory and pro-nociceptive IL-6 and IL-18 were found in all four patients (compared to a reference panel), whereas pro-apoptotic SCGF-β and TRAIL were higher only in the patients with the FHM1 mutation. Also, cytokines CXCL1, HGF, LIF, and MIF were found particularly high in the two mutation carriers, suggesting a possible role of vascular impairment and neuroinflammation in disease pathogenesis. Notably, some “algesic” cytokines, such as β-NGF and TNFβ, remained unchanged or even were down-regulated. Conclusion: We present a detailed genetic, neurological, and biochemical characterization of a small Russian FHM1 family and revealed evidence for higher levels of specific cytokines in migraine patients that support migraine-associated neuroinflammation in the pathology of migraine

Testing Genes Implicated in the Novel Case of Familial Hemiplegic Migraine

© 2016, Springer Science+Business Media New York.Familial hemiplegic migraine (FHM) is a rare monogenetic form of migraine associated with aura and motor dysfunctions. Molecular mechanisms of FHM still remain unknown; however, genetic predisposition to the disease has been suggested. We report several cases of FHM diagnosed in three generations of ethnic Tatars, Russian Federation. Apart from clear family character, patients presented with typical features of FHM including aura and ataxia. In order to determine disease genetic markers in these cases, we sequenced several genes (CACNA1A, ATP1A2, and SCN1A) previously reported in FHM. Sequence analysis demonstrated absence of the previously identified mutations in genes studied. This is the first genetic study of FHM in the Tatar population. The lack of known FHM associated mutation in these patients suggests presence of yet unidentified mutations in some other genes. Further studies including full genome sequencing are needed to clarify the genetic background of FHM cases in the Tatar population

Testing Genes Implicated in the Novel Case of Familial Hemiplegic Migraine

© 2016, Springer Science+Business Media New York.Familial hemiplegic migraine (FHM) is a rare monogenetic form of migraine associated with aura and motor dysfunctions. Molecular mechanisms of FHM still remain unknown; however, genetic predisposition to the disease has been suggested. We report several cases of FHM diagnosed in three generations of ethnic Tatars, Russian Federation. Apart from clear family character, patients presented with typical features of FHM including aura and ataxia. In order to determine disease genetic markers in these cases, we sequenced several genes (CACNA1A, ATP1A2, and SCN1A) previously reported in FHM. Sequence analysis demonstrated absence of the previously identified mutations in genes studied. This is the first genetic study of FHM in the Tatar population. The lack of known FHM associated mutation in these patients suggests presence of yet unidentified mutations in some other genes. Further studies including full genome sequencing are needed to clarify the genetic background of FHM cases in the Tatar population

Testing Genes Implicated in the Novel Case of Familial Hemiplegic Migraine

© 2016, Springer Science+Business Media New York.Familial hemiplegic migraine (FHM) is a rare monogenetic form of migraine associated with aura and motor dysfunctions. Molecular mechanisms of FHM still remain unknown; however, genetic predisposition to the disease has been suggested. We report several cases of FHM diagnosed in three generations of ethnic Tatars, Russian Federation. Apart from clear family character, patients presented with typical features of FHM including aura and ataxia. In order to determine disease genetic markers in these cases, we sequenced several genes (CACNA1A, ATP1A2, and SCN1A) previously reported in FHM. Sequence analysis demonstrated absence of the previously identified mutations in genes studied. This is the first genetic study of FHM in the Tatar population. The lack of known FHM associated mutation in these patients suggests presence of yet unidentified mutations in some other genes. Further studies including full genome sequencing are needed to clarify the genetic background of FHM cases in the Tatar population