Конечностно-поясная мышечная дистрофия с аутосомно- доминантным типом наследования: пельвиофеморальная форма Лейдена–Мебиуса

The paper considers current approaches to the clinical laboratory diagnosis of limb-girdle muscular dystrophy with emphasis on its autosomal dominant forms. The authors describe their clinical observation of a case of late diagnosis of the pelvifemoral form of autosomal dominant limbgirdle muscular dystrophy in a 37-year-old patient.В статье рассматриваются современные подходы к клинико-лабораторной диагностике конечностно-поясной мышечной дистрофии с акцентом на аутосомно-доминантные формы заболевания. Авторами представлено собственное клиническое наблюдение случая с поздней диагностикой пельвиофеморальной формы конечностно-поясной мышечной дистрофии с аутосомно-доминантным типом наследования у пациентки 37 лет.

Analysis of <i>SLC26A4, FOXI1,</i> and <i>KCNJ10</i> Gene Variants in Patients with Incomplete Partition of the Cochlea and Enlarged Vestibular Aqueduct (EVA) Anomalies

Pathogenic variants in the SLC26A4, FOXI1, and KCNJ10 genes are associated with hearing loss (HL) and specific inner ear abnormalities (DFNB4). In the present study, phenotype analyses, including clinical data collection, computed tomography (CT), and audiometric examination, were performed on deaf individuals from the Sakha Republic of Russia (Eastern Siberia). In cases with cochleovestibular malformations, molecular genetic analysis of the coding regions of the SLC26A4, FOXI1, and KCNJ10 genes associated with DFNB4 was completed. In six of the 165 patients (3.6%), CT scans revealed an incomplete partition of the cochlea (IP-1 and IP-2), in isolation or combined with an enlarged vestibular aqueduct (EVA) anomaly. Sequencing of the SLC26A4, FOXI1, and KCNJ10 genes was performed in these six patients. In the SLC26A4 gene, we identified four variants, namely c.85G>C p.(Glu29Gln), c.757A>G p.(Ile253Val), c.2027T>A p.(Leu676Gln), and c.2089+1G>A (IVS18+1G>A), which are known as pathogenic, as well as c.441G>A p.(Met147Ile), reported previously as a variant with uncertain significance. Using the AlphaFold algorithm, we found in silico evidence of the pathogenicity of this variant. We did not find any causative variants in the FOXI1 and KCNJ10 genes, nor did we find any evidence of digenic inheritance associated with double heterozygosity for these genes with monoallelic SLC26A4 variants. The contribution of biallelic SLC26A4 variants in patients with IP-1, IP-2, IP-2+EVA, and isolated EVA was 66.7% (DFNB4 in three patients, Pendred syndrome in one patient). Seventy-five percent of SLC26A4-biallelic patients had severe or profound HL. The morphology of the inner ear anomalies demonstrated that, among SLC26A4-biallelic patients, all types of incomplete partition of the cochlea are possible, from IP-1 and IP-2, to a normal cochlea. However, the dominant type of anomaly was IP-2+EVA (50.0%). This finding is very important for cochlear implantation, since the IP-2 anomaly does not have an increased risk of “gushers” and recurrent meningitis

A Systematic Review and Meta-Analysis of Free Triiodothyronine (FT3) Levels in Humans Depending on Seasonal Air Temperature Changes: Is the Variation in FT3 Levels Related to Nonshivering Thermogenesis?

Thyroid hormones play a crucial role in regulating normal development, growth, and metabolic function. However, the controversy surrounding seasonal changes in free triiodothyronine (FT3) levels remains unresolved. Therefore, the aim of this study was to conduct a systematic review and meta-analysis of variations in FT3 levels in relation to seasonal air temperatures in the context of current knowledge about its role in nonshivering thermogenesis. Ten eligible articles with a total of 336,755 participants were included in the meta-analysis. The studies were categorized into two groups based on the air temperature: “Cold winter”, where the winter temperature fell below 0 °C, and “Warm winter”, where the winter temperature was above 0 °C. The analysis revealed that in cold regions, FT3 levels decreased in winter compared to summer (I2 = 57%, p 2 = 28%, p < 0.001). These findings suggest that seasonal variations in FT3 levels are likely to be influenced by the winter temperature. Considering the important role of the FT3 in the nonshivering thermogenesis process, we assume that this observed pattern is probably related to the differences in use of thyroid hormones in the brown adipose tissue during adaptive thermogenesis, which may depend on intensity of cold exposure

A new approach to estimating the prevalence of hereditary hearing loss: An analysis of the distribution of sign language users based on census data in Russia.

The absence of comparable epidemiological data challenges the correct estimation of the prevalence of congenital hearing loss (HL) around the world. Sign language (SL) is known as the main type of communication of deaf people. We suggest that the distribution of SL can be interpreted as an indirect indicator of the prevalence of congenital HL. Since a significant part of congenital HL is due to genetic causes, an assessment of the distribution of SL users can reveal regions with an extensive accumulation of hereditary HL. For the first time, we analyzed the data on the distribution of SL users that became available for the total population of Russia by the 2010 census. Seventy-three out of 85 federal regions of Russia were ranked into three groups by the 25th and 75th percentiles of the proportion of SL users: 14 regions-"low proportion"; 48 regions-"average proportion"; and 11 regions-"high proportion". We consider that the observed uneven prevalence of SL users can reflect underlying hereditary forms of congenital HL accumulated in certain populations by specific genetic background and population structure. At least, the data from this study indicate that the highest proportions of SL users detected in some Siberian regions are consistent with the reported accumulation of specific hereditary HL forms in indigenous Yakut, Tuvinian and Altaian populations

The Russian Old-Settlers in the Arctic Coast of Eastern Siberia: Family Name Diversity in the Context of Their Origin

The populations of the Arctic Ocean coast in Eastern Siberia (Russia) are represented by a multicultural conglomerate of peoples of different origins: Paleo-Asiatic (Chukchi), Uralic (Yukaghirs), Tungusic (Evenks, Evens), Turkic (Yakuts, Dolgans), and Slavic (Russian explorers), who inhabited this territory during various historical periods. However, among the modern Arctic populations there are still “white spots”, such as people of the small village of “Russkoe Ust’ye”, who still have not been thoroughly studied. The main population consists of so called Russian old-settlers—the Russkoustinians. They traditionally distinguish their lineages into three groups identified by their time of settlement. First are the “Pomors”—who according to their legends are considered as the descendants of the first European colonists of the Age of Discovery, who settled the eastern shores of the Arctic Ocean in the 16th century before the inclusion of this territory in the Russian Empire in the early 17th century. Second are the “Cossacks”—who reached the Arctic during explorations of Siberia. The last are the “Zashiversk”—who arrived after the abolition of their hometown. In order to test these hypotheses, we analyzed modern family name diversity based on information on 62 individuals from 36 questionnaires. The analysis revealed that the “Pomors” lineages were presented in five families (43.5%), the “Cossacks” in one family (6.5%), and the “Zashiversk” in 37.1% of families. This fact indicates a probability that this village was founded by Russian Pomors who arrived there by the Northern Sea Routes before the official East Siberian colonization period

Agent-Based Modeling of Autosomal Recessive Deafness 1A (DFNB1A) Prevalence with Regard to Intensity of Selection Pressure in Isolated Human Population

An increase in the prevalence of autosomal recessive deafness 1A (DFNB1A) in populations of European descent was shown to be promoted by assortative marriages among deaf people. Assortative marriages became possible with the widespread introduction of sign language, resulting in increased genetic fitness of deaf individuals and, thereby, relaxing selection against deafness. However, the effect of this phenomenon was not previously studied in populations with different genetic structures. We developed an agent-based computer model for the analysis of the spread of DFNB1A. Using this model, we tested the impact of different intensities of selection pressure against deafness in an isolated human population over 400 years. Modeling of the &ldquo;purifying&rdquo; selection pressure on deafness (&ldquo;No deaf mating&rdquo; scenario) resulted in a decrease in the proportion of deaf individuals and the pathogenic allele frequency. Modeling of the &ldquo;relaxed&rdquo; selection (&ldquo;Assortative mating&rdquo; scenario) resulted in an increase in the proportion of deaf individuals in the first four generations, which then quickly plateaued with a subsequent decline and a decrease in the pathogenic allele frequency. The results of neutral selection pressure modeling (&ldquo;Random mating&rdquo; scenario) showed no significant changes in the proportion of deaf individuals or the pathogenic allele frequency after 400 years

A rare case of Waardenburg syndrome with unilateral hearing loss caused by nonsense variant c.772C>T (p.Arg259*) in the MITF gene in Yakut patient from the Eastern Siberia (Sakha Republic, Russia)

Waardenburg syndrome (WS) is an orphan genetic disease with autosomal dominant pattern of inheritance characterised by varying degrees of hearing loss accompanied by skin, hair and iris pigmentation abnormalities. Four types of WS differing in phenotypic characteristics are now described. We performed a Sanger sequencing of coding regions of genes PAX3, MITF, SOX10 and SNAI2 in the patient with WS from a Yakut family living in the Sakha Republic. No changes were found in the PAX3, SOX10 and SNAI2 coding regions while a previously reported heterozygous transition c.772C>T (p.Arg259*) in exon 8 of the MITF gene was found in this patient. This patient presents rare phenotype of WS type 2: congenital unilateral hearing loss, unilateral heterochromia of irises, and absence of skin/hair depigmentation and dystopia canthorum. Audiological variability in WS type 2, caused by the c.772C>T (p.Arg259*) variant in the MITF gene, outlines the importance of molecular analysis and careful genotype–phenotype comparisons in order to optimally inform patients about the risk of hearing loss. The results of this study confirm the association of pathogenic variants in the MITF gene with WS type 2 and expanded data on the variability of audiological features of the WS