This brief review presents scientific publications for the second quarter and early third quarter of 2025. The authors assessed studies on various topics: analysis of the results of whole-genome testing using biobanks and the relationship of identified variants with various disease phenotypes new artificial intelligence tool and statistical method that improve the efficiency of diagnostic search, accumulation of mutations in various cells, including oocytes, during life, description of the first patient in Russia with a hereditary disease, recently annotated in OMIM, BCARD syndrome. When compiling this digest, the authors' sphere of interest was not limited to a separate narrow area; they assessed the scale of the work carried out, its novelty, the results achieved, as well as the presentation of information about scientific work in the information field. At present, educational activities seem to be no less important for the full development of medical genetics and the integration of its methods into personalized medicine, than the scientific achievements themselves. The works presented in the digest received wide coverage not only from scientific and medical popular science portals, but also from leading Russian and foreign media outlets aimed at a wide audience.

Метод неинвазивного пренатального тестирования (НИПТ) получил широкое применение в клинической практике. Хотя показано положительное отношение к НИПТ как беременных женщин, так и медицинских работников, клиническое применение НИПТ привело к этическим дебатам с участием организаций пациентов, специалистов и представителей общественности. Этические проблемы, поднятые НИПТ, рассматриваются на основе ценностей свободного выбора, автономии и добровольного информированного согласия, избегания вреда, а также равенства, справедливости и инклюзивности. В представленной статье приведен обзор публикаций, посвященных защите автономии беременных и обеспечению осознанного информированного выбора при применении НИПТ в программах раннего пренатального скрининга. Non-invasive prenatal testing (NIPT) is increasingly used in clinical practice. Although positive attitudes toward NIPT have been shown among both pregnant women and health care providers, the clinical use of NIPT has led to ethical debate involving patient organizations, professionals, and the public. The ethical issues raised by NIPT are discussed in relation to the values of free choice, autonomy, free informed consent, avoidance of harm, and equality, fairness and inclusion. This article provides an overview of publications devoted to protecting the autonomy of pregnant women and ensuring informed choices in NIPT in early prenatal screening programs.

Сегодня результаты развития геномных технологий меняют подход к диагностике и лечению онкологических заболеваний. Так, клинические подходы к профилактике, диагностике и лечению рака молочной железы сместились в сторону использования молекулярно-генетической и иммуногистохимической информации. Целью настоящего обзора является описание возможностей применения различных молекулярно-генетических исследований опухолевой ткани с целью повышения эффективности лечения рака молочной железы. В обзоре обсуждаются результаты применения современных молекулярных (The Cancer Genome Atlas) и иммуногистохимических (суррогатных) маркеров, обеспечивающих разделение РМЖ по молекулярным подтипам, приведены преимущества и недостатки такого разделения. Представлены основные характеристики современных экспрессионных прогностических тестов, обсуждается целесообразность и сложности применения высокопроизводительного секвенирования, в том числе расширенных мультигенных NGS-панелей в клинической практике. Обзор предназначен для ординаторов и аспирантов, врачей-генетиков и врачей-онкологов, использующих в своей работе результаты современных молекулярно-генетических тестов.

Due to the intensive development of genetic research, the availability of genetic testing is increasing, including those based on genome-wide sequencing offered by private and public laboratories. Genetic testing can be used to identify the cause of the disease in patients with suspected hereditary (orphan) diseases and as a screening tool for healthy people, for example, if expectant parents planning to have children are carriers of hereditary diseases, to identify the risks of hereditary oncological diseases and multifactorial diseases, for pharmacogenetic testing, as well as for non-medical purposes, for example to determine the «ethnic origin». In addition, genetic research can be used to identify individuals, including in criminology and for genomic registration, determination of paternity and other kinship. This review paper analyzes some issues of terminology in the field of genetic research, including their results, as well as the legal basis for the genetic certification of the population of the Russian Federation, the use of the terms «genetic passport», «genetic profile» and «genomic passport», «genomic profile» and provides recommendations for improving the use of relevant terms such as standardizing the requirements for the preparation of a report/conclusion on the results of a genetic study and resolving the issue of the medical nature of the full-genome sequencing process. In addition, the practice of using the term «genetic passport» in federal acts, as well as domestic and foreign literature and media publications, is analyzed. Not only does the paper reveal the concept of complete genome sequencing, but also provides cases of mandatory medical and biological examination, including complete genome sequencing.

Неинвазивный пренатальный тест (НИПТ) – современный молекулярно-генетический метод, применяемый для скрининга хромосомной патологии у плода путем выделения и секвенирования свободно циркулирующих фрагментов ДНК плода и плаценты в крови матери (внеклеточная фетоплацентарная ДНК). НИПТ стал активно применяться в клинической практике сравнительно недавно – с начала прошлого десятилетия, в связи с чем нет единого мнения и решений этических вопросов, связанных с тестированием. Селекция пола, формирование спектра выявляемых рисков, медико-генетическое консультирование, дискриминация детей с хромосомными аномалиями и их родителей, «рутинизация» метода – основные этические проблемы, с которыми сталкиваются врачи различных специальностей и пациенты. Влияние результата НИПТ на репродуктивный выбор семейных пар сложно недооценить, поэтому применение теста в системе пренатального скрининга требует особого внимания, консультирования и участия специалистов разных областей медицины и не только. Non-invasive prenatal testing (NIPT) is a molecular genetic method of assessing the risks of fetal chromosomal abnormalities from cell-free fetal DNA by isolating and sequencing cell-free fetal and placental DNA fragments in maternal blood (cell-free fetoplacental DNA). NIPT has been in use for the past decade, so as a consequence, there is still no consensus or solution regarding the ethical issues surrounding the testing. Gender selection, the range of risks assessed, genetic counseling, discrimination against children with chromosomal abnormalities and their parents, and the «routinization» of the method are the main ethical problems physicians of different specialties and patients face. The impact of NIPT results on the reproductive choices of couples is hard to underestimate, so the involvement of various medical and other specialists in the system of prenatal screening requires particular consultative attention and assistance.

Russia and other countries report an increase in the incidence of malignant neoplasms, and approximately 10 % of all oncological cases have hereditary background. Molecular genetic testing in patients with diagnosed malignant neoplasms and a suspected hereditary factor will help to select effective modern methods of treatment and prevention of the development of neoplasms of other localizations. According to the study, 12,6 % of patients had hereditary cancer syndrome, which allowed to administer molecular genetic tests to patients’ relatives. Consequently, it becomes possible to detect hereditary cancer risk factors, improve the efficiency of clinical examination, elaborate and implement programs for prevention and early detection of the disease.

Актуальность. Благодаря непрерывному развитию и совершенствованию генетических методов исследований, расширяется спектр возможных пренатально устанавливаемых хромосомных аномалий. Применение современных молекулярно-генетических методов – неинвазивного пренатального теста (НИПТ) и хромосомного микроматричного анализа (ХМА) – позволяет как заподозрить, так и диагностировать хромосомные перестройки, которые невозможно определить стандартным цитогенетическим исследованием. Пациенты и методы. Представлены два клинических случая хромосомной перестройки у плода. Беременным женщинам выполнен пренатальный скрининг I триместра и полногеномный НИПТ. По показаниям проведена инвазивная пренатальная диагностика (ИПД), полученный материал направлен на цитогенетическое исследование и ХМА. Результаты. По результатам пренатального скрининга I триместра пациентки отнесены в группу высокого риска хромосомной аномалии (ХА) плода в обоих случаях. Высокий риск редких ХА установлен по результатам НИПТ. С согласия пациенток проведена ИПД. По результатам цитогенетических исследований и ХМА определен несбалансированный кариотип с наличием дополнительного генетического материала у плодов. Выводы. Применение современных молекулярно-генетических методов в дополнение к традиционным (пренатальному скринингу I триместра и стандартному цитогенетическому исследованию) позволяет увеличить спектр выявляемых ХА, определяемых пренатально. Background. Due to the continuous development and improvement of genetic research methods, the range of possible prenatally determined chromosomal abnormalities is expanding. The use of modern molecular genetic methods, the noninvasive prenatal testing (NIPT) and chromosomal microarray analysis (CMA), allows both the suspicion and diagnosis of chromosomal rearrangements that cannot be identified by standard cytogenetic testing. Patients and methods. Two clinical cases of fetal chromosomal rearrangement are presented. Pregnant women underwent the first trimester prenatal screening and whole-genome NIPT. When indicated, invasive prenatal diagnosis (IPD) was performed, and the obtained material was sent for cytogenetic examination and CMA. Results. Based on the results of prenatal screening in the first trimester of pregnancy, the patients were assigned to the high-risk group for fetal chromosomal abnormalities (CA) in both cases. A high risk of rare CA was established by the results of NIPT. IPD was performed with the consent of the patients. The results of cytogenetic studies and CMA determined an unbalanced karyotype with the presence of additional genetic material in the fetuses. Conclusions. The use of modern molecular genetic methods in addition to traditional methods (the first trimester prenatal screening and standard cytogenetic analysis) allows us to increase the range of detectable CAs determined prenatally.

Genetic data plays an increasingly important role in modern medicine. Decrease in the cost of sequencing with subsequent increase in imputation accuracy, and the accumulation of large amounts of high-quality genetic data enable the creation of polygenic risk scores (PRSs) to perform genotype-phenotype associations. The accuracy of phenotype prediction primarily depends on the overall trait heritability, Genome-wide association studies cohort size, and the similarity of genetic background between the base and the target cohort. Here we utilized 8,664 high coverage genomic samples collected across Russia by "Evogen ", a Russian biomedical company, to evaluate the predictive power of PRSs based on summary statistics established on cohorts of European ancestry for basic phenotypic traits, namely height and BMI. We have demonstrated that the PRSs calculated for selected traits in three distinct Russian populations, recapitulate the predictive power from the original studies. This is evidence that GWAS summary statistics calculated on cohorts of European ancestry are transferable onto at least some ethnic groups in Russia.

Background: Germinal pathogenic variants are the cause of the development of hereditary cancer syndromes (HCS). Various genetic tests are used for HCS detect, from the «frequent» mutations of one or several genes analysis to the full-length gene sequence, next-generation sequencing (NGS) based panel, whole exome (WES) or whole genome sequencing (WGS).There are some HCS cases with atypical clinical manifestations and the family history does not allow one to suspect a specific HCS and limit oneself to the study of only one or a few genes. Conducting research using NGS to assess the selected sample of cancer patient’s genetic characteristics has revealed atypical HCS cases.Aim: To present the WGS diagnosis results for two atypical hereditary tumor syndromes cases.Materials and methods: DNA isolation was performed using Qiagen DNA Isolation kit. WGS for all samples was performed at DNBSEQ-T7 (MGI) and DNBSEQ-G400 (MGI) sequencing platforms using PCR-free protocol with average sample coverage 30x. A standard bioinformatics analysis pipeline was implemented for all the samples data processing.Potential clinically relevant variants were validated using Sanger sequencing. For all patients was received signed a written consent.Results: In the first case report, a pathogenic variant in the TP53 gene was identified: c. 637C > T, p. Arg213Ter, rs397516436, and Li – Fraumeni syndrome was confirmed. In the second case, we detected two pathogenic variants carrier — BRCA2: c. 6644_6647del, p. Tyr2215SerfsTer13, rs80359616 and MSH2: c. 1906G > C, p. Ala636Pro, rs63750875 associated with hereditary breast and ovarian cancer and hereditary colorectal cancer (Lynch syndrome).Conclusion: NGS, including WGS makes it easier to identify all clinically significant germline variants associated with hereditary cancer syndromes in cancer patients, as well as to trace their segregation in relatives.

A description of a patient with a rare form of Camurati-Engelmann Disease (CED), also known as progressive diaphyseal dysplasia, manifested by gait disturbance, pain in the limbs and muscle weakness is presented. It is only ca. 300+ patients with this disease have been described worldwide to date. It was discovered in various ethnic groups regardless of gender. A clinical case observation of this disease with molecular genetic confirmation of the diagnosis is presented for the first time in a Russian language scientific periodical. Establishing an accurate diagnosis in the described observation became possible only thanks to the use of a modern molecular genetic method, Next-generation sequencing (NGS). The clinical case observed in the article showed non-specificity of symptoms in this disease. It would be impossible to establish an accurate diagnosis without the use of top notch, modern genetic technologies in this case. The absence of specific symptoms coupled with the late manifestation of the disease suggest that not all of the cases of this disease are detected and diagnosed.

Информация, полученная при генетическом тестировании, рассматривается как часть информации о здоровье, но она имеет особый статус, обусловленный ее прогностическим характером, возможностями обнаружения вариантов последовательности ДНК, имеющих отношение к здоровью человека в будущем, но не связанных с первоначальной целью тестирования, потенциальными изменениями интерпретации результатов теста по мере накопления научных знаний, а также с семейным характером. Из-за сложности интерпретации генетической информации и возможных медицинских, психологических и социальных последствий, связанных с генетическим тестированием, требуется получение информированного согласия пациентов или их законных представителей, а также медико-генетическое консультирование до и после тестирования. В обзоре обсуждаются особенности генетической информации и соответствующие особенности информированного согласия при генетическом и геномном тестировании, хранении генетической информации и биообразцов, скрининге новорожденных. Information obtained from genetic testing is considered as a part of health information, but it has a special status due to its predictive nature, the ability to detect DNA sequence variants that are relevant to human health in the future, but not related to the original purpose of testing, potential changes in interpretation test results as scientific knowledge accumulates, as well as with a family character. Due to the complexity of interpreting genetic information and the potential medical, psychological, and social implications associated with genetic testing, informed consent is required from patients or their legal representatives, as well as genetic counseling before and after testing. The review discusses the features of genetic information and the corresponding features of informed consent in genetic and genomic testing, storage of genetic information and biosamples, and newborn screening.

Non-invasive prenatal testing (NIPT) is a molecular genetic method of cell-free fetal DNA fetal chromosomal abnormalities risks assessing. Currently, NIPT is quite widespread throughout the world, and its clinical efficacy high sensitivity and specificity has been repeatedly proven. At the same time, the decision to include NIPT in the algorithm of prenatal diagnostics carried out with public funds depends on its cost-effectiveness, which should be assessed separately for each country or territory due to different costs and different models of inclusion. This article presents the different countries approaches to the assessment of the medical and economic efficiency of NIPT.

Cowden syndrome is a rare disease characterized by multiple hamartomas and increased breast, thyroid, kidney and uterine neoplasm risk. The lifetime breast cancer risk for patients with Cowden syndrome is 85 %, with an average age of diagnosis between 38 and 46 years. The diagnostic criteria for Cowden syndrome have been established by the International Cowden Consortium (ICC) and the National Comprehensive Cancer Network (NCCN), and are regularly revised, but the diagnosis of Cowden syndrome remains difficult due to the variety of phenotypic and clinical features of the disease. At the same time, the genetic variants associated with Cowden syndrome analysis is not a standard for patients with breast cancer.Objective: To demonstrate the non‑BRCA hereditary breast cancer detection using whole genome sequencing on the Cowden syndrome clinical case example.Materials and methods: The article describes a clinical case of a 37‑year‑old female patient with breast cancer, normal intelligence and phenotype, structural abnormalities of the thyroid gland (multinodular goiter). Whole genome sequencing was used to identify clinically significant genetic variants associated with hereditary tumor syndromes.Clinical case: The article presents a brief literature review on the clinical presentation of Cowden syndrome and indications for its molecular diagnosis. Also, the presented clinical case describes patient R., 37 years old female with breast cancer, who underwent treatment in the City Clinical Oncological Hospital № 1 of the Moscow City Health Department in 2021. The patient was fully examined and enrolled in the whole genome sequencing project under the Order № 69 of Moscow Healthcare Department dated February 1, 2021 «Oncogenetic research organization in Moscow». The results revealed a pathogenic variant in the PTEN gene, previously associated with Cowden syndrome.Conclusion: The use of whole genome sequencing allows to identify hereditary tumor syndromes, the clinical manifestation of which may be breast cancer.

AbstractBackgroundA fast adoption of a non–invasive prenatal testing (NIPT) in clinical practice is a global tendency last years. Firstly, in Russia according a new regulation it was possible to perform a widescale testing of pregnant women in chromosomal abnormality risk. The aim of the study—to assess efficiency of using NIPT as a second-line first trimester screening test in Moscow.MethodsBased on the first trimester combined prenatal screening results 12,700 pregnant women were classified as a high-risk (cut-off ≥ 1:100) and an intermediate-risk (cut-off 1:101 – 1:2500) groups followed by whole genome NIPT. Women from high-risk group and those who had positive NIPT results from intermediate-risk group were considered for invasive prenatal diagnostic.Results258 (2.0%) samples with positive NIPT results were detected including 126 cases of trisomy 21 (T21), 40 cases of T18, 12 cases of T13, 41 cases of sex chromosome aneuploidies (SCAs) and 39 cases of rare autosomal aneuploidies (RAAs) and significant copy number variations (CNVs). Statistically significant associations (p < 0.05) were revealed for fetal fraction (FF) and both for some patient’s (body mass index and weight) and fetus’s (sex and high risk of aneuploidies) characteristics. NIPT showed as a high sensitivity as specificity for common trisomies and SCAs with an overall false positive rate 0.3%.ConclusionsNIPT demonstrated high sensitivity and specificity. As a second-line screening test it has shown a high efficiency in detecting fetus chromosomal anomalies as well as it could potentially lower the number of invasive procedures in pregnant women.

Abstract BackgroundA fast adoption of a non–invasive prenatal testing (NIPT) in clinical practice is a global tendency last years. The aim of the study - to assess efficiency of using NIPT as a second-line first trimester screening test in Moscow.MethodsBased on the results of the first trimester combined prenatal screening 12700 pregnant women were classified as a high-risk (cut-off ≥1:100) and an intermediate-risk (cut-off 1:101 – 1:2500) groups followed by whole genome NIPT. Women from high-risk group and those who had positive NIPT results were considered for invasive prenatal diagnostic. Results258 (2,0%) samples with positive NIPT results were detected including 126 cases of trisomy 21 (T21), 40 cases of T18, 12 cases of T13, 41 cases of sex chromosome aneuploidies (SCAs) and 39 cases of rare autosomal aneuploidies (RAAs) and significant copy number variations (CNVs). Statistically significant associations (p<0.05) were revealed for fetal fraction (FF) and both for some patient’s (body mass index and weight) and fetus’s characteristics (sex and high risk of aneuploidies). NIPT showed high sensitivity and specificity for common trisomies and SCAs with an overall false positive rate 0.3%.ConclusionsNIPT demonstrated high sensitivity and specificity. As a second-line screening test it has shown high efficiency in detecting fetus chromosomal anomalies as well as it could potentially lower the number of invasive procedures in pregnant women.