The Genetic Spectrum of Cystic Fibrosis in Different Populations

Аннотация

Cystic fibrosis (CF) is a hereditary disease caused by mutations in the CFTR gene, which regulates chloride ion transport in epithelial cells. To date, more than 1,500 CFTR mutations have been identified, with their prevalence varying among different ethnic groups. This article reviews data on the frequency and spectrum of CFTR mutations in various populations, including Iran, Turkey, Russia, the USA, Australia, and Europe. Special attention is given to neonatal CF screening programs, their effectiveness, challenges related to false-negative results, and the need to adapt mutation panels based on ethnic characteristics. Studies confirm that expanding genetic panels, lowering IRT threshold values, and implementing a differentiated screening approach can significantly improve diagnostic accuracy and patient outcomes. Keywords: Cystic fibrosis, children, lungs, CFTR gene. (CF) among newborns ranges from 1:600 to 1:1200, Introduction: To date, more than 1,500 mutations in with approximately 300 children diagnosed with CF the CFTR gene have been identified, with their annually in Russia. In recent years, due to early prevalence varying among different ethnic groups. neonatal screening and improved therapy, the average Several studies have been conducted in Iran to examine life expectancy of CF patients has increased from 5 to the distribution of CFTR mutations among cystic 40 years in developed countries and up to 23 years in fibrosis (CF) patients. In northeastern Iran, an analysis Moscow and St. Petersburg (4). of 56 patients identified 24 mutant alleles (21.42%), with the most common being ΔF508 (10.71%) (1). In Russia, the most common mutation is F508del, found Another study in Mazandaran Province found only one in over 60% of patients. However, more than 1,200 mutation, ΔF508, among 30 CF patients, accounting for CFTR gene mutations have been identified, including 21.7% (2). Similarly, an analysis of CFTR mutations in 70 rare regional variants such as L138ins in the Middle Iranian patients showed that ΔF508 was present in Urals (5) and c.1545_1546del in Chechnya (6). 17.8% of alleles, N1303K in 4.3%, and G542X in 3.6% A study conducted in Turkey revealed that the (3). prevalence of CF in Central Anatolia is similar to that in The CFTR gene is located on chromosome 7 (locus Northern Europe, with an incidence rate of 2.9 per 7q31) and encodes the cystic fibrosis transmembrane 10,000 live births in Konya and 2.8 per 10,000 in conductance regulator, which controls chloride ion Kayseri. Among 30 CF patients, the F508del mutation transport. Mutations in this gene lead to thickened was the most frequent (17/30), with half of the patients secretions from exocrine glands, causing dysfunction in being homozygous and the other half compound the respiratory, digestive, and reproductive systems heterozygous (7). (4). A comparative study in Australia evaluated three According to WHO data, the incidence of cystic fibrosis neonatal screening strategies between 1989 and 2008. American Journal Of Biomedical Science & Pharmaceutical Innovation 11 https://theusajournals.com/index.php/ajbspi American Journal of Applied Science and Technology (ISSN: 2771-2745) It was found that incorporating a CFTR 12-mutation detected. However, a study by McGarry et al. (2024) panel increased diagnostic sensitivity from 86.6% revealed significant racial and ethnic disparities in NBS (using only IRT) to 95.8% (8). sensitivity. Asian (OR 6.3) and Black infants (OR 2.5) were more likely to receive false-negative results, In the United States, the newborn screening program attributed to low IRT levels or incomplete mutation for cystic fibrosis (CF NBS) has evolved over two panels. The introduction of an expanded CFTR panel decades. An analysis of false-negative cases in New covering 402 variants improved CF detection across all Jersey revealed that some patients with severe racial and ethnic groups. respiratory diseases were not detected during initial testing. This led to an update of the CF NBS algorithm, The spectrum of CFTR mutations in cystic fibrosis (CF) which now includes a lower IRT threshold and an patients of Pakistani origin differs significantly from expanded panel covering 139 CFTR variants (9). Western populations. A study by Majid et al. (2025) reported a high frequency of rare mutations, In the U.S., expanded CFTR panels include up to 402 emphasizing the need to adapt screening programs for mutations; however, high false-negative rates persist this ethnic group. among Asian and African American populations (10). The prevalence of CRMS/CFSPID varies by geographic In Australia, a study by Lee & Orton (2025) found that region and the neonatal screening (NBS) algorithms the sensitivity of CFTR panels among South Asians was used. A study conducted in six Italian centers found that 64%, the lowest among all ethnic groups. In Europe, the the ratio of CF patients to infants with CRMS/CFSPID prevalence of the F508del mutation is higher amon