Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to lymphoid malignancies. The majority of NBS patients are identified with a homozygous five base pair deletion in the Nibrin (NBN) gene (c.657_661del5, p.K219fsX19) with a founder effect observed in Caucasian European populations, especially of Slavic origin. We present here an analysis of a cohort of 136 NBS patients of Eastern Slav origin across Belarus, Ukraine, Russia, and Latvia with a focus on understanding the geographic distribution, incidence of malignancy, and treatment outcomes of this cohort. Our analysis shows that Belarus had the highest prevalence of NBS (2.3 per 1,000,000), followed by Ukraine (1.3 per 1,000,000), and Russia (0.7 per 1,000,000). Of note, the highest concentration of NBS cases was observed in the western regions of Belarus and Ukraine, where NBS prevalence exceeds 20 cases per 1,000,000 people, suggesting the presence of an “Eastern Slavic NBS hot spot.” The median age at diagnosis of this cohort ranged from 4 to 5 years, and delay in diagnosis was more pervasive in smaller cities and rural regions. A total of 62 (45%) patients developed malignancies, more commonly in males than females (55.2 vs. 34.2%; p=0.017). In 27 patients, NBS was diagnosed following the onset of malignancies (mean age: 8 years). Malignancies were mostly of lymphoid origin and predominantly non-Hodgkin lymphoma (NHL) (n=42, 68%); 38% of patients had diffuse large B-cell lymphoma. The 20-year overall survival rate of patients with malignancy was 24%. However, females with cancer experienced poorer event-free survival rates than males (16.6% vs. 46.8%, p=0.036). Of 136 NBS patients, 13 underwent hematopoietic stem cell transplantation (HSCT) with an overall survival of 3.5 years following treatment (range: 1 to 14 years). Indications for HSCT included malignancy (n=7) and immunodeficiency (n=6). Overall, 9% of patients in this cohort reached adulthood. Adult survivors reported diminished quality of life with significant physical and cognitive impairments. Our study highlights the need to improve timely diagnosis and clinical management of NBS among Eastern Slavs. Genetic counseling and screening should be offered to individuals with a family history of NBS, especially in hot spot regions.

We present the first comprehensive report on the distribution and genotype-phenotype correlations of CF-causing mutations in Western Ukraine (former Galicia). The 2184insA mutation was identified in 17 unrelated CF patients, 2 of whom are homozygotes for this allele. This mutation is associated with the classical form of CF. The high frequency of 2184insA mutation (7.20% of all mutated CF chromosomes) suggests that it is likely of Galician origin, from where it has spread throughout Europe and beyond. The achieved 83.71% mutation detection rate fulfills the minimal pre-requisite for introduction of the "two-tier" (IRT/DNA) newborn screening program.

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Severe combined immunodeficiency (SCID) is a group of inborn errors of immunity (IEI) characterized by severe T-and/or B-lymphopenia. At birth, there are usually no clinical signs of the disease, but in the first year of life, often in the first months the disease manifests with severe infections. Timely diagnosis and treatment play a crucial role in patient survival. In Ukraine, the expansion of hemostatic stem cell transplantation and the development of a registry of bone marrow donors in the last few years have created opportunities for early correction of IEI and improving the quality and life expectancy of children with SCID. For the first time in Ukraine, we initiated a pilot study on newborn screening for severe combined immunodeficiency and T-cell lymphopenia by determining T cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs). The analysis of TREC and KREC was performed by real-time polymerase chain reaction (RT-PCR) followed by analysis of melting curves in neonatal dry blood spots (DBS). The DBS samples were collected between May 2020 and January 2022. In total, 10,350 newborns were screened. Sixty-five blood DNA samples were used for control: 25 from patients with ataxia-telangiectasia, 37 -from patients with Nijmegen breakage syndrome, 1with X-linked agammaglobulinemia, 2with SCID (JAK3 deficiency and DCLRE1C deficiency). Retest from the first DBS was provided in 5.8% of patients. New sample test was needed in 73 (0.7%) of newborns. Referral to confirm or rule out the diagnosis was used in 3 cases, including one urgent abnormal value. CID (T low B+NK+) was confirmed in a patient with the urgent abnormal value. The results of a pilot study in Ukraine are compared to other studies (the referral rate 1: 3,450). Approbation of the Frontiers in Immunology frontiersin.org 01

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Introduction. Infertility is the problem of almost 15 % of married couples. Half of the cases is caused by a «male factor». Commonly, idiopathic oligo and azoospermia are diagnosed in these cases. Genetic reasons of spermatogenesis failure, such as numerical or structural chromosome anomalies and gene mutations that are responsible for fertility often depend on ethnic background of patients [1][2][3][4][5][6][7][8][9][10].Karyotype abnormalities are observed in 4.6 % of men with oligospermia and in 13.7 % patients with azoospermia. Structural chromosomal anom alies are detected in 5.1 % of infertile men, besides, autosomal translocations are the most common in men with oligospermia and changes in gonosomes (sex chromosomes) are more characteristic for persons with azoospermia [10].The genes located on the Y chromosome play an essential role in the control and regulation of spermatogenesis. Microdeletions of AZF locus are one of the most widespread genetic causes of infer tility in men with severe spermatogenetic failure: microdeletions in AZF are diagnosed in 5-11 % individuals with azoospermia, while in oligosper mia -in 2-8 % of cases [4,7,9]. In 12 % of infer tile men mutations of CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene are detected. Furthermore, in these cases uni or bilat eral congenital absence of the vas deferens (CAVD) can be revealed [11].Consequently, previously described genetic factors have the leading role in etiology dysfunc tions of male reproductive system. That is why the purpose of the study was to set the frequency and the spectrum of the chromosomal anomalies, microdeletions of AZF region of Y chromosome and CFTR gene mutations among infertile men from Ukraine.Materials and methods. Eighty idiopathically infertile males, selected out of 260 infertile men, attending the Prycarpatian Center of Human Reproductions, were included in the study. The diagnosed cases of anatomic defects, infectious dis eases, endocrine, immunological infertility were excluded from the studied group. The age of these individuals ranged from 25 to 43 years. An experi enced urologist carried out a detailed anamnesis and clinical examination of every patient. Sperm analysis was performed at least twice at appropriate interval. Based on spermatological analysis results, infertile were subdivided into three groups: 36 (45 %) patients with aspermia (AS), 19 (24 %) patients

Gastroesophageal disease (GERD) is the one of most spread diseases that injures an esophagus. Taking into account the large number of factors that can cause GERD development already in child age, including genetic predisposition, it is necessary to analyze each of them in detail. Aim of this work was to analyze a frequency and possible association type of р. Leu72Met mutation of GHRL gene in children with gastroesophageal reflux disease. The analysis of clinical parameters and course of disease in the group of 100 schoolchildren with GERD was carried out. The molecular-genetic study of c.214C>A locus of GHRL gene by CPR method (rs696217) was carried out in patients with GERD and 40 healthy children from the control group. In 82% of children with GERD was revealed a GHRL 214СС (Leu/Leu) homozygous genotype, at 58% among children from the control group. GHRL 214СА (Leu/ Met) genotype was registered three times more seldom in children of the studied group comparing with ones from the control group: 15,0% and 42,5%, respectively. It was established, that GHRL 214CС genotype presence conditions the increase of GERD development risk in 3,4 times. On the contrary, GHRL 214CА genotype manifests a reliable protective effect that is essentially decreased GERD development risk in a child at such genotype – 0,24 comparing with a conventional unit. There was established alleles and genotypes distribution of c.214C>A (р.Leu72Met) locus of GHRL gene in children with GERD. GHRL 214CС genotype is associated with threefold increase of GERD risk development. Gender differences as to GERD development risk at different genotypes of ghrelin gene were established. At GHRL 214СС (Leu/Leu) genotype the relative GERD risk for boys increased in more than 6 times. There were not established any differences in alleles and genotypes distribution depending on erosive or surface inflammatory changes of a gastrointestinal tract mucosa.