Liddle syndrome due to a novel mutation in the γ subunit of the epithelial sodium channel (ENaC) in family from Russia: a case report.

BACKGROUND: Liddle syndrome is a monogenic disease with autosomal dominant inheritance. Basic characteristics of this disease are hypertension, reduced concentration of aldosterone and renin activity, as well as increased excretion of potassium leading to low level of potassium in serum and metabolic alkalosis. The cause of Liddle syndrome is missense or frameshift mutations in SCNN1A, SCNN1B, or SCNN1G genes that encode epithelial sodium channel subunits. CASE PRESENTATION: We describe a family with Liddle syndrome from Russia. 15-year-old proband has arterial hypertension, hypokalemia, hyporeninemia, metabolic alkalosis, but aldosterone level is within the normal range. At 12 years of age, arterial hypertension was noticed for the first time. We identified novel frameshift mutation c.1769delG (p.Gly590Alafs) in SCNN1G, which encodes the γ subunit of ENaC in vertebrates. The father and younger sister also harbor this heterozygous deletion. Treatment with amiloride of proband and his sister did not normalize the blood pressure, but normalized level of plasma renin activity. CONCLUSIONS: Our results expand the mutational spectrum of Liddle syndrome and provide further proof that the conserved PY motif is crucial to control of ENaC activity. Genetic analysis has implications for the management of hypertension, specific treatment with amiloride and counselling in families with Liddle syndrome.

Probiotics and autoprobiotics for treatment of Helicobacter pylori infection.

The article discusses various approaches for probiotic treatment of Helicobacter pylori (H. pylori) infection: Probiotics as an adjuvant treatment in the standard eradication therapy; probiotic strains as a monotherapy; and autoprobiotics as a monotherapy. Autoprobiotics refer to indigenous bifidobacteria, lactobacilli, or enterococci isolated from a specific individual, intended to restore his/her microbiota and improve his/her health. The potential mechanisms of probiotic action against H. pylori include correction of the gut microbiota, immunological effects (enhancement of humoral and cellular immunity, and reduction of oxidative stress), direct antagonistic effects against H. pylori (such as colonization resistance and bacteriocin synthesis), and stimulation of local immunological protection (strengthening of the mucous protective barrier and reduction of gastric mucosa inflammation). The incorporation of probiotics into comprehensive eradication therapy shows promise in optimizing the treatment of H. pylori infection. Probiotics can enhance the eradication rates of H. pylori, reduce the occurrence and severity of side effects, and improve patient compliance. Probiotic or autoprobiotic monotherapy can be considered as an alternative treatment approach in cases of allergic reactions and insufficient effectiveness of antibiotics. We recommend including probiotics as adjunctive medications in anti-H. pylori regimens. However, further randomized multicenter studies are necessary to investigate the effects of probiotics and autoprobiotics against H. pylori, in order to gain a better understanding of their mechanisms of action.

Neuronal ceroid lipofuscinosis in the Russian population: Two novel mutations and the prevalence of heterozygous carriers.

BACKGROUND: Neuronal ceroid lipofuscinoses (NCLs) are a group of neurodegenerative disorders characterized by an accumulation of lipofuscin in the body's tissues. NCLs are associated with variable age of onset and progressive symptoms including seizures, psychomotor decline, and loss of vision. METHODS: We describe the clinical and molecular characteristics of four Russian patients with NCL (one female and three males, with ages ranging from 4 to 5 years). The clinical features of these patients include cognitive and motor deterioration, seizures, stereotypies, and magnetic resonance imaging signs of brain atrophy. Exome sequencing was performed to identify the genetic variants of patients with NCL. Additionally, we tested 6,396 healthy Russians for NCL alleles. RESULTS: We identified five distinct mutations in four NCL-associated genes of which two mutations are novel. These include a novel homozygous frameshift mutation in the CLN6 gene, a compound heterozygous missense mutation in the KCTD7 gene, and previously known mutations in KCTD7, TPP1, and MFSD8 genes. Furthermore, we estimated the Russian population carrier frequency of pathogenic and likely pathogenic variants in 13 genes associated with different types of NCL. CONCLUSION: Our study expands the spectrum of mutations in lipofuscinosis. This is the first study to describe the molecular basis of NCLs in Russia and has profound and numerous clinical implications for diagnosis, genetic counseling, genotype-phenotype correlations, and prognosis.