BackgroundCystic fibrosis (CF) is one of the most common life-threatening genetic disorders. Around 2000 variants in the CFTR gene have been identified, with some proportion known to be pathogenic and 300 disease-causing mutations have been characterized in detail by CFTR2 database, which complicates its analysis with conventional methods.MethodsWe conducted next-generation sequencing (NGS) in a cohort of 89 adult patients negative for p.Phe508del homozygosity. Complete clinical and demographic information were available for 84 patients.ResultsBy combining MLPA with NGS, we identified disease-causing alleles in all the CF patients. Importantly, in 10% of cases, standard bioinformatics pipelines were inefficient in identifying causative mutations. Class IV-V mutations were observed in 38 (45%) cases, predominantly ones with pancreatic sufficient CF disease; rest of the patients had Class I-III mutations. Diabetes was seen only in patients homozygous for class I-III mutations. We found that 12% of the patients were heterozygous for more than two pathogenic CFTR mutations. Two patients were observed with p.[Arg1070Gln, Ser466*] complex allele which was associated with milder pulmonary obstructions (FVC 107 and 109% versus 67%, CI 95%: 63-72%; FEV 90 and 111% versus 47%, CI 95%: 37-48%). For the first time p.[Phe508del, Leu467Phe] complex allele was reported, observed in four patients (5%).ConclusionNGS can be a more information-gaining technology compared to standard methods. Combined with its equivalent diagnostic performance, it can therefore be implemented in the clinical practice, although careful validation is still required.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0328-z) contains supplementary material, which is available to authorized users.

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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.

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