BackgroundCystic fibrosis (CF; OMIM #219700) is a common autosomal recessive disease caused by pathogenic variants (henceforward mutations) in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The spectrum and frequencies of CFTR mutations vary among different populations. Characterization of the specific distribution of CFTR mutations can be used to optimize genetic counseling, foster reproductive choices, and facilitate the introduction of mutation-specific therapies. Chechens are a distinct Caucasian ethnic group of the Nakh peoples that originated from the North Caucasus. Chechens are one of the oldest ethnic groups in the Caucasus, the sixth largest ethnic group in the Russian Federation (RF), and constitute the majority population of the Chechen Republic (Chechnya). The spectrum of CFTR mutations in a representative cohort of Chechen CF patients and healthy individuals was analyzed.MethodsMolecular genetic analysis of 34 CFTR mutations (representing approx. 80–85% of mutations in multiethnic CF populations of the RF) was performed in 32 CF patients from 31 unrelated Chechen families living in Chechnya. One hundred randomly chosen healthy Chechens were analyzed for the 15 most common “Russian” mutations. The clinical symptoms in Chechen CF patients with different CFTR genotypes were investigated.ResultsHigh frequencies of c.1545_1546delTA (p.Tyr515X; 1677delTA) (52 out of 64 CFTR alleles tested; 81.3%) and c.274G > A (p.Glu92Lys, E92K) (8/64, 12.5%) mutations were found. Twenty patients were homozygous for the c.1545_1546delTA mutation, and eight were compound heterozygous for the c.1545_1546delTA and c.274G > A mutations. Three carriers of the c.1545_1546delTA mutation were also found in the cohort of 100 apparently healthy Chechens (frequency – 0.015). The c.1545_1546delTA and c.274G > A mutations are linked to the same haplotype (22–7–16–13) of intragenic Short Tandem Repeat markers, i.e., IVS1CA, IVS6aGATT, IVS8CA, and IVS17bCA.ConclusionsThe distribution of CFTR mutations in the Chechen CF population is unique regarding the high frequency of mutations c.1545_1546delTA and c.274G > A (more than 90% of the mutant alleles). The c.274G > A mutation is associated with a less severe course of CF than that observed in c.1545_1546delTA homozygotes. Testing for these two variants can be proposed as the first step of CF DNA diagnosis in the Chechen population.

Since the beginning of the COVID-19 epidemic, the European cystic fibrosis society (ECFS) has decided to launch a special ECFS-COVID-19 program to collect information on the of COVID-19 characteristics in the patients with cystic fibrosis (CF). The results of the program should help timely and efficiently provide the patients with CF with the necessary care. Initially, it was assumed that COVID-19 would be severe in CF patients. The aim. Тo assess the prevalence and characteristics of COVID-19 in patients with cystic fibrosis (CF) in the Russian Federation (RF). Methods. 6 cases (4 children and 2 adults) of COVID-19 in Russian CF patients were analyzed. Results. There are 405,843 infected with SARS-CoV-2 in Russia, the incidence of coronavirus infection in Russia was 1.4 cases per 1 thousand people. According to the Ministry of Health of the RF, as of December 2019, there were 3,931 patients with CF (2,823 children and 1,108 adults). The incidence of COVID-19 was 1.5 per 1000 patients with CF (1.4 : 1,000 for children and 1.8 : 1,000 for adults). The incidence was not higher than in the General population. The diagnosis of COVID-19 was confirmed in 4 boys and 2 women, 3 of the patients were infected with Pseudomonas aeruginosa and 2 – with Achromobacter spp. Mild disease was seen in 5 patients including all the children. Pneumonia was registered in 3 patients. One child with COVID-19 had abdominal syndrome. 2 patients – 1 adult and 1 child – needed in-patient care. Additional antibiotics were given to 4 patients, 2 of them received i/v antibiotics. One adult patient was on the lung transplantation waiting list. This woman had long-term oxygen therapy and BiPAP noninvasive respiratory support before the infection with SARS-CoV-2, FEV1 was 24 %pred. Conclusion. Despite the fact that patients with CF are at risk of severe COVID-19, to date, in the described cases, COVID-19 infection has not led to a significant deterioration of the symptoms of CF. Not a single fatal outcome in Russian patients with CF has been recorded.

Кистозный фиброз-наследственное заболевание, возникающее в результате мутаций в гене регулятора трансмембранного транспорта ионов хлора (CFTR). Установление мутаций в гене CFTR необходимо для выявления клинических особенностей кистозного фиброза. Цель исследования: выявить генотип-фенотипические корреляции между мутациями первого класса патогенности и клиническими проявлениями кистозного фиброза на основе изучения распространенности и структуры мутаций гена CFTR.

No abstract