A Novel Cystic Fibrosis Gene Mutation C.4242+1G>C in an Omani Patient: A Case Report

Cystic fibrosis (CF) is a genetic disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that affects multisystems in the body, particularly the lungs and digestive system. We report a case of an Omani newborn who presented with meconium ileus and high suspicion of CF. Thus, full CFTR gene sequencing was performed, which revealed a homozygous unreported C.4242+1G>C novel gene mutation. Both parents were found to be heterozygous for this mutation. This case sheds light on the importance of the extensive genetic testing of typical CF cases in the absence of family history or during neonatal presentations, especially when the sweat test cannot be performed and the diagnosis can be challenging.

Spermogram parameters and genetic abnormalities

The prevalence of genetic abnormalities in men with infertility is 5.8% (n = 9766), of which 4.2% are sex chromosome abnormalities and 1.5% are autosomal abnormalities. In the Russian Federation, this indicator varies from 4.72% (n = 539) (Novosibirsk) to 10.78% (n = 204) (St. Petersburg, the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott) — the percentage of detectability probably depends on the concentration of patients in specialized institutions. Given the high frequency of genetic abnormalities in infertile men, it is necessary to correctly select diagnostic methods in accordance with the specifi c clinical situation. When the concentration of spermatozoa decreases to less than 10 million/ml, karyotyping is recommended; at a concentration of less than 5 million/ml, the search for AZF deletions is necessary; in severe disorders of spermatogenesis — the detection of mutations in the cystic fibrosis gene (CFTR). To confirm genetically determined asthenozoospermia, the electron microscopy of spermatozoa is required. Taking into account the development of assisted reproductive technologies, including the active use of intracytoplasmic sperm injection and the relationship of sperm pathology with severe genetically determined diseases, it is necessary to inform potential parents what risks to the health of future children the use of such material carries.

Cystic fibrosis gene mutations and polymorphisms in Saudi men with infertility

ABSTRACT BACKGROUND: Some mutations of the cystic fibrosis transmembrane regulator ( CFTR ) gene may impair spermatogenesis or cause a congenital absence of the vas deferens that manifests as isolated male infertility. OBJECTIVE: Assess the frequency and analyze the spectrum of CFTR gene variations in Saudi men with primary infertility. DESIGN: Prospective, cross-sectional. SETTING: Tertiary care specialist hospital in Jeddah. PATIENTS AND METHODS: Genomic DNA was extracted from peripheral blood samples of Saudi men who presented with primary infertility to the outpatient andrology clinic with either azoospermia or oligoasthenoteratozoospermia. Polymerase chain reaction and direct sequencing were used to identify all variants of the CFTR gene. MAIN OUTCOME MEASURES: Proportion of the patients with a mutant CFTR gene and the spectrum of CFTR gene variations. SAMPLE SIZE: 50 infertile Saudi men. RESULTS: This study identified 10 CFTR gene variants in 7 (14%) subjects (100 chromosomes). The detected variants and polymorphisms were: c.1408G>A, c.4389G>A, c.2562T>G, c.869+11C>T, c.2909-92G>A, c.3469-65C>A, c.1210-6delT, c.1210-6T>A, c.2988+1G>A, and c.1210-13GT>TG. CONCLUSION: We demonstrated that 14% of the study subjects had one or more CFTR mutations and these were compounded in most of the affected patients. The spectrum of CFTR gene mutations in these subjects was similar to the mutations reported in other studies throughout the world. LIMITATIONS: Small sample size and the lack of a control group. CONFLICTS OF INTEREST: None.

Investigation of the properties of the oral liquid and polymorphism of the MUC5B gene in children with cystic fibrosis

Investigation of the properties of the oral liquid and polymorphism of the MUC5B gene in children with cystic fibrosis Nazaryan R., Tkachenko M.,Volkova N. The article presents the study of biophysical and biochemical properties of saliva and polymorphism of the MUC5B protein gene in children with cystic fibrosis. It has been determined that the development of chronic gingivitis in children with cystic fibrosis occurs of the background of a saliva elasticity increasing and of the salivation rate decreasing. The presence of the allele of MUC5B gene with 9 repeats (59 bp) in the intron 36 in the genotype for cystic fibrosis patients is likely to indicate a lower tendency to gingivitis, while among patients possessing the allele with 6 repeats in the genotype the higher percentage of moderately severe gingivitis was detected. These data could be used to predict the development of chronic gingivitis, depending on the genetic polymorphism of the MUC5B gene and to form risk groups for the purpose of differentiated prescribing preventive and therapeutic measures. Keywords: children, cystic fibrosis, gene polymorphism, gingivitis, oral fluid. Резюме. ДОСЛІДЖЕННЯ ВЛАСТИВОСТЕЙ РОТОВОЇ РІДИНИ І ПОЛІМОРФІЗМУ ГЕНУ MUC5B У ХВОРИХ НА МУКОВІСЦИДОЗ ДІТЕЙ Назарян Р. С., Ткаченко М. В., Волкова Н. Є. Проведено дослідження біофізичних та біохімічних властивостей ротової рідини та поліморфізму гена білка MUC5B у хворих на муковісцидоз дітей. Визначено, що розвиток хронічного гінгівіту у дітей з муковісцидозом відбувається на тлі підвищення показників тягучості ротової рідини та зниження швидкості слиновиділення. Алельні варіанти кількості повторів 59 п.н. у інтроні 36 гена MUC5B можуть вказувати на схильність пацієнтів до розвитку різного ступеню тяжкості гінгівіту. Результати дослідження можуть бути використані з діагностичною та прогностичною метою і диференційованого призначення профілактичних та лікувальних заходів. Ключові слова: гінгівіт, діти, муковісцидоз, поліморфізм генів, ротова рідина. Резюме. ИССЛЕДОВАНИЕ СВОЙСТВ РОТОВОЙ ЖИДКОСТИ И ПОЛИМОРФИЗМА ГЕНА MUC5B У БОЛЬНЫХ МУКОВИСЦИДОЗОМ ДЕТЕЙ Назарян Р. С., Ткаченко М.В., Волкова Н. Е. Проведено исследование биофизических и биохимических свойств ротовой жидкости и полиморфизма гена белка MUC5B у больных муковисцидозом детей. Определено, что развитие хронического гингивита у детей с муковисцидозом происходит на фоне повышения показателей тягучести ротовой жидкости и снижения скорости слюноотделения. Аллельные варианты количества повторов 59 п.н. в интроне 36 гена MUC5B могут указывать на склонность пациентов к развитию гингивита различной степени тяжести. Результаты исследования могут быть использованы с диагностической и прогностической целью и дифференцированного назначения профилактических и лечебных мероприятий. Ключевые слова: гингивит, дети, муковисцидоз, полиморфизм генов, ротовая жидкость.

CYSTIC FIBROSIS: A BREAKTHROUGH IN 21ST-CENTURY THERAPY

The review presents new data on the latest advances in the treatment of cystic fibrosis, a rare genetic disease. The methods used were literature search in the Scopus, Web of Science, and EMBASE databases. The importance of a number of drugs prescribed for anti-inflammatory purposes (ibuprofen, azithromycin) is discussed, data from multicenter studies of new drugs are presented. The role of mucolytic agents and the need to develop new antibacterial compounds are shown. Particular attention in the review is given to the development of new targeted therapies for cystic fibrosis. The data of studies of ivacaftor, lumacactor, tezacactor in this category of patients are presented, as well as a spectrum of mutations of the cystic fibrosis gene in which these molecules can be prescribed. The experience of the use of correctors in adult patients with cystic fibrosis in the Russian Federation is described, the effectiveness and safety of the long-term use of these drugs are described.