Whole exome sequencing links dental tumor to an autosomal-dominant mutation in ANO5 gene associated with gnathodiaphyseal dysplasia and muscle dystrophies.

Tumors of the jaws may represent different human disorders and frequently associate with pathologic bone fractures. In this report, we analyzed two affected siblings from a family of Russian origin, with a history of dental tumors of the jaws, in correspondence to original clinical diagnosis of cementoma consistent with gigantiform cementoma (GC, OMIM: 137575). Whole exome sequencing revealed the heterozygous missense mutation c.1067G > A (p.Cys356Tyr) in ANO5 gene in these patients. To date, autosomal-dominant mutations have been described in the ANO5 gene for gnathodiaphyseal dysplasia (GDD, OMIM: 166260), and multiple recessive mutations have been described in the gene for muscle dystrophies (OMIM: 613319, 611307); the same amino acid (Cys) at the position 356 is mutated in GDD. These genetic data and similar clinical phenotypes demonstrate that the GC and GDD likely represent the same type of bone pathology. Our data illustrate the significance of mutations in single amino-acid position for particular bone tissue pathology. Modifying role of genetic variations in another gene on the severity of the monogenic trait pathology is also suggested. Finally, we propose the model explaining the tissue-specific manifestation of clinically distant bone and muscle diseases linked to mutations in one gene.

[The load and diversity of hereditary diseases in four raions of Rostov oblast].

The results of a medical genetic survey of the population of four raions (176 535 individuals) of Rostov oblast (Dubovsky, Zimovnikovsky, Myasnikovsky, and Krasnosulinsky raions) are presented. The load of autosomal dominant (AD), autosomal recessive (AR), and X-linked hereditary diseases for urban and rural population was calculated, and the diversity of monogenic hereditary diseases (MHD) was reviewed. The nosological spectrum of MHD constituted 117 diseases (63 diseases with AD inheritance; 38 with AR inheritance; and 16 with X-linked inheritance). The analysis showed that the incidence of MHD among the population of Rostov oblast was 1 : 336. Considerable differentiation in the prevalence rates of MHD (AD, AR, and X-linked pathologies) among certain raions was revealed.

[Epidemiology of monogenic hereditary diseases in Rostov oblast: population dynamic factors determining the differentiation of the load of hereditary diseases in eight districts].

Analysis of the diversity of monogenic hereditary diseases in eight raions (districts) of Rostov oblast (region) of Russia (Tsimlyansk, Volgodonskoi, Tselina, Egorlykskaya, Millerovo, Tarasovskaya, Rodionovo-Nesvetaiskaya, and Matveevo-Kurgan raions) has been summarized. The total sample size was 320925 subjects. The spectrum of hereditary diseases detected in the eight districts comprises 187 diseases, including 99 autosomal dominant (AD), 72 autosomal recessive (AR), and 16 X-linked diseases. The mean prevalence rate of each disease in the total population has been calculated. Accumulation of individual diseases in different regions of Rostov oblast has been calculated; the disease accumulation has been compared with that in some populations of Russia examined earlier. Cluster analysis using the data on the frequencies of genes of hereditary diseases has shown the gene geographic position of the Rostov oblast population among the following ethnic populations of Russia: Russians (Kostroma, Kirov, and Rostov oblasts and Krasnodar krai), Chuvashes (Chuvashia), Adygeans (Adygea), Maris (Marii El), and Udmurts (Udmurtia).

[Epidemiology of monogenic hereditary diseases in Rostov Oblast: population dynamic factors determining the differentiation of the load of hereditary diseases in eight districts].

A genetic epidemiological study has been carried out in eight raions (districts) of Rostov oblast (region) of Russia: Tsimlyansk, Volgodonskoi, Tselina, Egorlykskaya, Millerovo, Tarasovskaya, Rodionovo-Nesvetaiskaya, and Matveevo-Kurgan raions. The population structure (the parameters of the isolation by distance model, ethnic assortative marriage, random inbreeding (F(ST), endogamy index, and ie) and the genetic demographic characteristics of the regional population (vital statistics, Crow's index, and its components) have been analyzed. The total sample size was 320925 subjects (including 114106 and 206816 urban and rural residents, respectively). The load of the main types of Mendelian diseases (autosomal dominant (AD), autosomal recessive (AR), and X-linked diseases) has been calculated for the total sample from eight districts and separately for the urban and rural populations. Substantial differences between individual districts in the AD and AR genetic loads have been found, especially upon separation into urban and rural samples. The results of correlation analysis suggest that migration and genetic drift are the main factors of genetic differentiation of populations with respect to the prevalence of hereditary diseases.

[Analysis of population genetic structure of ten district populations of the Rostov oblast by means of an extended isonymic method of Barrai and colleagues].

Parameters suggested by Barrai et al. (1992), including the random isonymy (I(r)), surname diversity (alpha), migration index (nu), and entropy (H) and redundancy (R) of surname distribution have been estimated in ten district populations of the Rostov oblast. Their weighted mean values are the following: I(r) = 0.000813, nu = 0.048, alpha = 1334.9, H = 11.30, R = 22.52.

[Medical genetic study of the Rostov oblast population: analysis of surname distribution in seven districts].

Data on the surname frequency distribution in seven districts (districts) of the Rostov oblast (region) have been used to calculate random inbreeding varying from 0.000064 to 0.000186 in the Volgodonsk and Millerovo districts, respectively. Schematic surname landscapes have been constructed for six districts. The observed spectrum of frequent surnames is compared with that of the complete register of surnames in Russia.

[The marriage migration characteristics of the Rostov oblast population].

Marriage records have been used to study the marriage migration structure of five raions of the Rostov oblast. The mean ethnic marriage assortativeness in the Russian and Ukrainian rural populations are 1.16 and 1.6, respectively. The endogamy index of the urban population varies from 0.19 to 0.34; and that of the rural population, from 0.21 to 0.54. Malecot's isolation by distance parameters have been calculated. Genetic landscapes have been constructed.

[Medical genetic study of the Rostov Oblast population: changes in reproductive parameters with time]. / Mediko-geneticheskoe obsledovanie naseleniia rostovskoi oblasti: vremennaia dinamika reproduktivnykh parametrov.

Changes in vital statistics and Crow's indices during the past 50 years have been studied on the basis of answers to 2165 questionnaires divided into five groups according to the age of women surveyed.

[Clinical polymorphism of Shereshevsky-Turner syndrome in Rostov region and Northern Caucasus in 1978-1998]. / Klinicheskii polimorfizm sindroma Shereshevskogo-Ternera u zhitelei Rostovskoi oblasti i Severnogo Kavkaza (1978-1998 gg).

Polymorphism of Shereshevsky-Turner syndrome (STS) was studied in 233 patients who were examined at medical genetic services of the Research Institute of Obstetrics and Pediatrics (Rostov-on-Don) and Rostov Regional Hospital from 1978 to 1998. The subjects examined were residents of the Rostov oblast (administrative region) (RO) and some settlements in the northern Caucasus (NC). The mean incidence rate of STS was 3.8 per 10,000 newborns in this region in the period studied. Most STS cases were accounted for by the X trisomy (60 and 66.6% in the RO and NC, respectively). The mosaic form of STS was found in 25% of cases in both RO and NC. Other cytogenetic forms were found in 13.5 and 8.33% of patients from the RO and NC, respectively. The clinical polymorphism of STS, dynamics of its manifestation during ontogeny, and anthropometric parameters of the patients were studied. The effects of the age of parents, the season and month of conception, occupational hazards at the parents' workplaces, and the place of residence on the risk of STS were analyzed. Factor analysis was used to determine the sets of the main clinical signs characteristic of different STS cytogenetic forms in the RO and NC populations.