[Clinical and epidemiological characteristics of hereditary motor-sensory neuropathy 1X caused by the mutation c. 259C> G (p. P87A) in the GJB1 gene of patients from the Republic of Bashkortostan]. / Kliniko-épidemiologicheskie kharakteristiki nasledstvennoi motorno-sensornoi neiropatii 1Kh tipa, obuslovlennoi mutatsiei s. 259S>G (r. R87A) v gene GJBI, u patsientov Respubliki Bashkortostan.

BACKGROUND: Hereditary motor-sensory neuropathy 1X (НМСН 1X) is the second frequent form of hereditary motor-sensory neuropathies caused by mutations in the GJB1 gene (gap junction B1 type). The authors have established earlier that the с.259C>G (р.P87A) mutation is the most frequent cause of НМСН 1Ð¥ (92%) in patients from the Republic of Bashkortostan. AIM: To study in details the territorial ethnic distribution and clinical manifestations of the с.259C>G (р.P87A) in the GJB1 gene in patients with НМСН 1Ð¥ from the Republic of Bashkortostan. MATERIAL AND METHODS: Clinical/neurological data were assessed in 52 patients (32 men and 20 women) from 13 families with this НМСН 1Ð¥ mutation in accordance to the diagnostic criteria of the European neuromuscular center. Twenty-three patients underwent standard electroneuromyographic study ('Nicolet Viking quest') using cutaneous electrodes. Data analysis was performed with Statistica ver.6.0 ('Stat Soft, Inc.', 2003) software. RESULTS: The с.259C>G (р.P87A) mutation was more frequent in Bashkir (61%) and Russian (31%) families from 6 areas of the Republic of Bashkortostan. The age-at-onset was 13.24±4.33 years in men. In women, the age-at-onset varied from 7 to 45 years, it was difficult to detect this parameter in several patients due to the absence of complaints and symptoms of disease. A comparative analysis revealed the higher degree of peripheral nerve lesions in men compared to women. There was the distinct difference in electrophysiological parameters (excitation spreading velocity and M-response amplitude) along motor fibers of the middle nerves between men and women that indicated the predominantly demyelinating character of the pathological process in men and the axonal character in women. CONCLUSION: Clear clinical/electrophysiological sex differences (intra- and inter family) were shown in patients with НМСН IX with the с.259C>G (р.P87A) mutation in the GJB1 gene. The disease was less severe and often with the absence of symptoms in women. Genetic testing for mutations in the GJB1 gene, including the с.259C>G (р.P87A) mutation, can be recommended to female patients with excitation spreading velocity >38m/s.

[Role of Allelic Genes of Matrix Metalloproteinases and Their Tissue Inhibitors in the Peptic Ulcer Disease Development].

Peptic ulcer disease is a chronic disease of the gastrointestinal tract, mainly manifesting itself in the formation of the fairly persistent ulcer defect of the mucous membrane of the stomach and/or duodenum. Association analysis of common polymorphisms of matrix metalloproteinases genes MMP-1 (rs1799750, rs494379), MMP-2 (rs2285052), MMP-3 (rs3025058), MMP-9 (rs3918242, rs17576), and MMP-12 (rs2276109) and their tissue inhibitors TIMP-2 (rs8179090) and TIMP-3 (rs9619311) was carried out in 353 patients with a gastric ulcer or duodenal ulcer and in 325 unrelated healthy individuals from the Republic of Bashkortostan. Associations of polymorphic variants rs1799750 and rs494379 of gene MMP-1, rs3025058 of gene MMP-3, rs3918242 and rs17576 of gene MMP-9, and rs9619311 of gene TIMP-3 with the risk of peptic ulcer disease in Russians and Tatars were revealed.

[Two novel mutations in gene SPG4 in patients with autosomal dominant spastic paraplegia].

Hereditary spastik paraplegias (HSP) are a group of neurodegenerative disorders with primary lesion of the pyramidal tract. The most frequent autosomal dominant form of the disease in Europeans is HSP associated with mutations in the spastin gene (SPG4). Analysis of the gene SPG4 was carried out in 52 unrelated families with HSP from Bashkortostan by SSCP and following sequencing. Previously undescribed frameshift mutations c.322del29 (p.Val108SerfsX18) and c.885del10 (p.Thr295ThrfsX16) were detected in two unrelated families. Clinical studies have shown that, in both families, the disease corresponds to an uncomplicated form of hereditary spastic paraplegia, a main feature of which is the lower spastic paraparesis without any other symptoms.

[Association of cytokine gene polymorphisms in peptic ulcer development in the Bashkortostan Republic].

Peptic ulcer disease (PUD) is a chronic disease based on recurrent gastric or duodenal ulcers. Association analysis of common polymorphisms of the cytokines genes IL1B (rs1143634), IL1RN (rs71941886), IL8 (rs4073), IL10 (rs1800872), and TNFA (rs1800629) was conducted in 254 patients with gastric ulcer or duodenal ulcer and in 277 unrelated healthy individuals from the Bashkortostan Republic. Associations of the rs1143634C allele and the C/C genotype of the IL1B gene with PUD in ethnic Bashkirs have been revealed. The frequency of the rs4073A/A genotype of the IL8 gene was significantly higher in the control group as compared to patients infected with H. pylori. Our results confirm the significant role of rs1143634 of the IL1B gene in PUD development.

[MFN2 gene analysis in patients with hereditary motor and sensory neuropathy from Bashkortostan Republic].

Hereditary motor and sensory neuropathy (HMSN) type IIA is caused by mutations in the mitofusin type-2 (MFN2) gene and represents one of the most common axonal forms of HMSN. We determined the spectrum and frequency of MFN2 gene mutations in patients from the Bashkortostan Republic (BR). Four different mutations were revealed in 5 out of 170 unrelated patients, i.e., c.2113G>A (p.Val705Ile) (1.2% among all types of H MSN in the total sample of patients and 2% among patients of Tatar ethnicity). This mutation was described previously; c.775C>T (p.Arg259Cys) (0.6%, in the total sample of patients and 2% among the patients of Tatar ethnicity); c.776G>A (p.Arg259His) (0.6% in the total sample of patients and 1.5% among the patients of Russians ethnicity); and c.2171T>C (p.Leu724Pro) (1.2% in the total sample of patients and 7.4% among the patients of Bashkirs ethnicity). These are new mutations that were not observed among healthy family members and in control samples of healthy subjects. Five identified nucleotide substitutions represent single nucleotide polymorphisms of the gene, including c.892G>A (p.Gly298Arg), c.957C>T (Gly319Gly), and c1039-222t>c, which were described previously, while c.175+28c>t and c.2204+15t>c represent new nucleotide substitutions in the intron regions of the gene.

Haplotype Diversity and Reconstruction of Ancestral Haplotype Associated with the c.35delG Mutation in the GJB2 (Cx26) Gene among the Volgo-Ural Populations of Russia.

The mutations in theGJB2(Сх26) gene make the biggest contribution to hereditary hearing loss. The spectrum and prevalence of theGJB2gene mutations are specific to populations of different ethnic origins. For severalGJB2 mutations, their origin from appropriate ancestral founder chromosome was shown, approximate estimations of "age" obtained, and presumable regions of their origin outlined. This work presents the results of the carrier frequencies' analysis of the major (for European countries) mutation c.35delG (GJB2gene) among 2,308 healthy individuals from 18 Eurasian populations of different ethnic origins: Bashkirs, Tatars, Chuvashs, Udmurts, Komi-Permyaks, Mordvins, and Russians (the Volga-Ural region of Russia); Byelorussians, Ukrainians (Eastern Europe); Abkhazians, Avars, Cherkessians, and Ingushes (Caucasus); Kazakhs, Uzbeks, Uighurs (Central Asia); and Yakuts, and Altaians (Siberia). The prevalence of the c.35delG mutation in the studied ethnic groups may act as additional evidence for a prospective role of the founder effect in the origin and distribution of this mutation in various populations worldwide. The haplotype analysis of chromosomes with the c.35delG mutation in patients with nonsyndromic sensorineural hearing loss (N=112) and in population samples (N =358) permitted the reconstruction of an ancestral haplotype with this mutation, established the common origin of the majority of the studied mutant chromosomes, and provided the estimated time of the c.35delG mutation carriers expansion (11,800 years) on the territory of the Volga-Ural region.