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 VOLUME Vol.05 Issue03 2025 

PAGE NO. 11-14 

DOI 10.37547/ajbspi/Volume05Issue03-03 

 
 
 
 

The Genetic Spectrum of Cystic Fibrosis in Different 

Populations 
 

Кhamidova Farida Muinova 

Samarkand State Medical University, Uzbekistan 

 

Hamraev Bekzod Zhuramurodovich 

Samarkand State Medical University, Uzbekistan 

 

Received: 13 January 2025; Accepted: 26 February 2025; Published: 13 March 2025 

 

Abstract: 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. 

 

Introduction: To date, more than 1,500 mutations in 
the CFTR gene have been identified, with their 
prevalence varying among different ethnic groups. 
Several studies have been conducted in Iran to examine 
the distribution of CFTR mutations among cystic 
fibrosis (CF) patients. In northeastern Iran, an analysis 
of 56 patients identified 24 mutant alleles (21.42%), 
with the most common being ΔF508 (10.71%) (1). 
Another study in Mazandaran Province found only one 
mutation, ΔF508, among 30 CF patients, accounting for 
21.7% (2). Similarly, an analysis of CFTR mutations in 70 
Iranian patients showed that ΔF508 was present in 
17.8% of alleles, N1303K in 4.3%, and G542X in 3.6% 
(3). 

The CFTR gene is located on chromosome 7 (locus 
7q31) and encodes the cystic fibrosis transmembrane 
conductance regulator, which controls chloride ion 
transport. Mutations in this gene lead to thickened 
secretions from exocrine glands, causing dysfunction in 
the respiratory, digestive, and reproductive systems 
(4). 

According to WHO data, the incidence of cystic fibrosis 

(CF) among newborns ranges from 1:600 to 1:1200, 
with approximately 300 children diagnosed with CF 
annually in Russia. In recent years, due to early 
neonatal screening and improved therapy, the average 
life expectancy of CF patients has increased from 5 to 
40 years in developed countries and up to 23 years in 
Moscow and St. Petersburg (4). 

In Russia, the most common mutation is F508del, found 
in over 60% of patients. However, more than 1,200 
CFTR gene mutations have been identified, including 
rare regional variants such as L138ins in the Middle 
Urals (5) and c.1545_1546del in Chechnya (6). 

A study conducted in Turkey revealed that the 
prevalence of CF in Central Anatolia is similar to that in 
Northern Europe, with an incidence rate of 2.9 per 
10,000 live births in Konya and 2.8 per 10,000 in 
Kayseri. Among 30 CF patients, the F508del mutation 
was the most frequent (17/30), with half of the patients 
being homozygous and the other half compound 
heterozygous (7). 

A comparative study in Australia evaluated three 
neonatal screening strategies between 1989 and 2008. 

 

https://doi.org/10.37547/ajbspi/Volume05Issue03-03
https://doi.org/10.37547/ajbspi/Volume05Issue03-03


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American Journal of Applied Science and Technology (ISSN: 2771-2745) 
 

 

It was found that incorporating a CFTR 12-mutation 
panel increased diagnostic sensitivity from 86.6% 
(using only IRT) to 95.8% (8). 

In the United States, the newborn screening program 
for cystic fibrosis (CF NBS) has evolved over two 
decades. An analysis of false-negative cases in New 
Jersey revealed that some patients with severe 
respiratory diseases were not detected during initial 
testing. This led to an update of the CF NBS algorithm, 
which now includes a lower IRT threshold and an 
expanded panel covering 139 CFTR variants (9). 

In the U.S., expanded CFTR panels include up to 402 
mutations; however, high false-negative rates persist 
among Asian and African American populations (10). 

In Australia, a study by Lee & Orton (2025) found that 
the sensitivity of CFTR panels among South Asians was 
64%, the lowest among all ethnic groups. In Europe, the 
prevalence of the F508del mutation is higher among 
Northern Europeans (95.6%) compared to Southern 
European populations (12). 

In Turkey, a national CF NBS program has been in place 
since 2015, based on a two-step measurement of 
immunoreactive trypsinogen levels (IRT-1/IRT-2). A 
study by Çoksüer et al. (2025) showed that this method 
has low sensitivity (80.3%) and a positive predictive 
value (PPV) of 23.3%, along with high rates of false-
negative (FNP) and false-positive results. Among 66 
infants diagnosed with CF, 19.7% were identified solely 
based on clinical suspicion, highlighting the need to 
revise IRT threshold values and explore alternative 
strategies to improve screening accuracy. 

In the French-speaking community of Belgium, an 
improved IRT-DNA screening algorithm has been 
implemented since 2020, incorporating a 12-variant 
CFTR panel and a fail-safe IRT/IRT method. A four-year 
evaluation (14) demonstrated a sensitivity of 95% and 
a median diagnosis age of 23 days, indicating a high 
level of early detection and timely treatment. 

In Italy, the incidence of cystic fibrosis (CF) among 
Caucasian newborns is estimated at 1/2500–1/3000. A 
study by Dell’Edera et al. (2014) analyzed the 
prevalence of CFTR mutations among CF patients and 
infertile couples in the Basilicata region. CFTR 
mutations were detected in 6.85% of individuals 
screened, exceeding the hypothetical carrier frequency 
(4%). While F508del was the most common cause of CF, 
rare regional mutations were also identified. The study 
highlighted the need for expanded screening panels to 
improve diagnostic accuracy and disease prevention. 

In the United States, neonatal screening is mandatory 
and includes IRT level measurement, a CFTR variant 
panel, and CFTR sequencing if a single variant is 

detected. However, a study by McGarry et al. (2024) 
revealed significant racial and ethnic disparities in NBS 
sensitivity. Asian (OR 6.3) and Black infants (OR 2.5) 
were more likely to receive false-negative results, 
attributed to low IRT levels or incomplete mutation 
panels. The introduction of an expanded CFTR panel 
covering 402 variants improved CF detection across all 
racial and ethnic groups. 

The spectrum of CFTR mutations in cystic fibrosis (CF) 
patients of Pakistani origin differs significantly from 
Western populations. A study by Majid et al. (2025) 
reported a high frequency of rare mutations, 
emphasizing the need to adapt screening programs for 
this ethnic group. 

The prevalence of CRMS/CFSPID varies by geographic 
region and the neonatal screening (NBS) algorithms 
used. A study conducted in six Italian centers found that 
the ratio of CF patients to infants with CRMS/CFSPID 
was 1:1.30, higher than in countries with a greater 
prevalence of the F508del mutation (18). In the United 
States, the frequency of CRMS is estimated to be higher 
than expected due to the inclusion of expanded gene 
sequencing in NBS protocols (21). 

Children with CRMS/CFSPID generally have a milder 
clinical course compared to those with a confirmed CF 
diagnosis. The Italian study (18, 19) found that infants 
with CRMS/CFSPID had significantly lower levels of 
immunoreactive trypsinogen (IRT) and sweat chloride 
concentrations, with the F508del mutation present in 
only 20% of alleles. 

Another study (20) demonstrated that by the age of 
seven, children with CRMS/CFSPID showed less severe 
lung involvement compared to CF patients. They 
experienced fewer hospitalizations, had better lung 
function, and had lower rates of complications such as 
Pseudomonas aeruginosa and Staphylococcus aureus 
infections. However, in 44% of these children, the 
diagnosis was later revised to CF, highlighting the need 
for careful long-term monitoring. 

Additionally, according to Barben et al. (2021), despite 
the generally favorable prognosis for most patients 
with CRMS/CFSPID, some may develop CF or CFTR-
related disorders (CFTR-RD) during adolescence or 
adulthood. Therefore, educating families about 
potential risks and disease symptoms is crucial. 

The lack of a standardized approach to managing 
children with CRMS/CFSPID has led to significant 
variations in clinical practice across different centers 
(18). For example, the frequency of sweat testing 
ranged from 8% to 100%, while recommendations for 
salt supplementation varied from 11% to 90%. 

The updated international guidelines (21) introduced a 



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American Journal of Applied Science and Technology (ISSN: 2771-2745) 
 

 

key recommendation for a detailed assessment of 
children with CRMS/CFSPID at the age of six. This 
evaluation includes lung function tests and chest 
imaging, allowing for informed decisions regarding 
further monitoring. Families are also advised to receive 
clear instructions on symptoms that require medical 
attention. 

In Uzbekistan, studies by Barataeva L. and Rakhmonova 
Sh. (2024) confirm that the intestinal form of CF is 
predominant among newborns. However, data on 
specific CFTR mutations in this region remain limited. 

Thus, the study of CFTR gene mutations across different 
populations demonstrates significant ethnic and 
geographic variations in their prevalence. Data on 
mutation frequencies are essential for optimizing 
newborn screening programs, prenatal testing, and 
genetic counseling. Advancements in diagnostic 
methods, including expanded mutation panels and 
lower IRT threshold values, contribute to earlier 
disease detection, which is crucial for improving patient 
outcomes. 

CONCLUSIONS 

1.The genetic variability of CFTR differs significantly by 
ethnicity, necessitating the adaptation of screening 
programs for various populations. 

2.The F508del mutation is the most common in Europe 
and Russia but is less frequent in Asia and among 
African Americans. Some regions have specific rare 
mutations. 

3.Neonatal CF screening programs have demonstrated 
varying effectiveness, with expanded mutation panels 
and lower IRT thresholds improving diagnostic 
sensitivity. 

4.The false-negative rate remains high among Asian 
and African American infants, highlighting the need to 
refine NBS algorithms. 

5.Patients with CRMS/CFSPID require long-term 
monitoring, as some may develop classical CF over 
time. 

6.Genetic studies and CFTR mutation analysis play a key 
role in optimizing screening, prenatal testing, and 
genetic counseling. 

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