Osteoporosis (OP) is one of the most common metabolic diseases of the skeleton, the frequency of which rises with age. OP is one of the leading causes of disability and a reduction in life expectancy in the elderly, thereby dealing with one of the most important public health problems around the world. A major role in the development of OP play both gender and genetic factors, there are gender and regional differences in the prevalence of the disease. Currently, there has been significant progress in detecting  the molecular pathogenesis of the disease, but studies of the genetic basis of OP are far from completion and there are many issues, which need further study. Understanding the epidemiology and pathogenesis of osteoporosis is necessary for the development of effective methods of presymptomatic diagnostics, treatment and prevention of diseases. The review is devoted to the systematization of the results of studies  on the genetic  aspects of OP and current trends  in further study of the problem.

The hereditary angioedema type I/II is included in group of orphan hereditary diseases for which there is an effective pathogenic treatment. The disease considerably  diminishes the quality of the patient life and quite often leads  to life threatening  conplaints and death.  According to foreign researches, almost all cases of the disease are caused by mutations in the SERPING1 gene.  In this work search  results of mutations in SERPING1 gene among 331 unrelated  family and isolated Russian cases with hereditary angioedema by using the Sanger sequencing and the quantitative MLPA for all gene exons are presented. Total of 91 mutations, which cause or possibly cause angioedema, in 112 cases were revealed. Among these mutations 48% were not published in literature earlier. Ten bening or likely bening variants of the gene are also found. In the spectrum of the SERPING1 mutations, missens-mutations prevail, deletions, splice site mutations and nonsence-mutations are often observed,  insertions, large deletions and indels is rarer. The analysis of the patient sample discovered  a twofold predominance of female among the patients  of the reason  requires an additional research.

An aberrant DNA methylation distribution is a functional event in the process of leukemogenesis and a target of epigenetic therapy. To identify DNA methylation markers most common for any molecular subtype of pediatric acute myeloid leukemia (AML) we have applied a method of unbiased differential methylation screening of the genomes and designed  multiplex MS-PCR system of DNA methylation markers belonging to the promoter regions of the genes  EGFLAM, TMEM176A/176B, GSG1L, CLDN7, CXCL14 and SOX8. The system has a sensitivity of 90—91% for determining the malignant process. We have studied bone marrow samples  from 39 children with AML. All patients were treated by decitabine and ATRA in complex with chemotherapy (CT). Methylation index (MI) was 0.197 ± 0.181 for patients with a myeloblasts content less than 40%, and 0.514 ± 0.222 for patients with myeloblasts content more than 40% (p = 0.000736). Methylation of the CLDN7, GSGL1 and EGFLAM genes is absent  in the group with low MI. Patients with the initial content of myeloblasts less than 40% demonstrate absence of methylation on the 15th day after the start of the CT. The average MI decreases in the group with the initially high content of myeloblasts due to decrease in the frequencies of methylation of the genes CXCL14, TMEM176A/176B, GSGL1 and SOX8. The 5-day course  of demethylation therapy is accompanied by an increase in the content of blast cells and an equalization of the methylation profile. With the marker system developed it is possible to evaluate the malignant progression of blast cells, which are considered morphologically normal after CT, demonstrating at the same time the abnormal methylation profile of tumor cells.

The load and diversity of monogenic hereditary diseases (HD) among the Russians of the Karachaevo-Cherkess Republic (KCR), living in 10 rural districts and two cities, have been studied. The total size of the investigated population of the Republic was 410,367 people,  including Russians  —  134,756.  In total, 385 Russian KCR patients  from 281 families were registered. Load AD, AR and X-linked diseases in rural districts  (3.01 ± 0.32,  1.98 ± 0.26 and 1.23 ± 0.29) are more than twice higher in cities (1.00 ± 0.10, 0.89 ± 0.09 and 0.42 ± 0.09). The diversity of HD was 99 nosological forms: 56 diseases with AD type of inheritance (193 patients from 126 families), 31 diseases with AR (152 patients  out of 124 families) and 12 diseases with X-linked type of inheritance (40 affected from 31 families). A comparative analysis of the diversity of AD and AR of the National AB with the previously studied populations / ethnos of the European part of Russia (Russians in 7 regions, 5 ethnic groups of the Volga-Ural and 5 ethnic groups of the North Caucasus) was conducted, showed that Russians in the KCR retained a significant similarity of the «pathological» gene pool with the Russians of others  populations and its difference from the same  gene pool of Karachays and Circassians.

Congenital muscular dystrophy (CMD) is a genetically heterogeneous group of diseases, the main clinical manifestation of which is the «floppy» child syndrome, characterized by muscle weakness that occurs immediately after birth or during the first six months of life. The merozin-deficiency muscular dystrophy, caused by mutations in the LAMA2 gene, is the most common form of CMD. This paper presents results of molecular genetic  analysis of the LAMA2 gene  in 29 unrelated  patients  with CMD. The spectrum  of LAMA2 gene  mutations  in Russia is described. New allelic variants of the LAMA2 gene  have been  detected: c.6992+1G>T,  c.3829C>T, c.5422C>T, c.6406C>T, c.7888C>T, c.172T>C, c.3dupG, c.4254insCCAT, c.4665dupG, c.7308insGATTGGCTATATCAATTGTATCTATA and c.7701delTinsGTGTCCCTAGGTGTCCCTA. The founder  effect  for the most  frequent in Russia mutation of the LAMA2 gene — c.7536delC  is shown, the most probable ancestral  haplotype for chromosomes with this mutation is determined.

Hereditary palmoplantar keratoderma (PPK) is characterized by hyperkeratosis  of the skin of palms and soles. PPK type Bothnia was described as having a high prevalence  in the 2 northernmost provinces of Sweden,  situated  to the west and the northwest of the Gulf of Bothnia. In Swedish families with dominant PPK researchers established that the phenotype  had been linked to the most frequent locus 12q13, but no mutations were found in KRT1. Various missense AQP5-mutations were found in all cases. A three-generation family of Chinese Han ethnicity with AQP5-PPK was described later. In a five-generations Russian PPK family the cause of the disease was searched using the linkage analysis, Senger  sequencing, MPS (IlluminaTruSeq® ExomeKit). We found a linkage to locus 12q13. The maximum Lod score of 3.69 was observed on D12S368 (52 631 kb). The area was limited within D12S1661 (48 607kb): Lod - 2.61    = 0 and D12S1586 (54 146 kb): Lod - 3.66     = 0. However, no mutation in KRT1 and over KRT’s genes of this region was revealed. We performed an exome analysis in one of the patients and identified three heterozygous variants in the target region. Two variants in CELA1 and OR8S1 genes did not segregate with the disease in the family and only one AQP5 c.369C>G(p.Asn123Lys) substitution could be a root of the PPC in this family (Lod max — 3.71   = 0.00). We confirmed that the cause of PPK could be mutations in the water-channel aquaporin-5 gene. Our findings have shown that AQP5-PPK can be found in different ethnic groups,  not only in Bothnia region.