Background: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene. The most severe, DeltaF508, mutation accounts for nearly 70% of CF cases worldwide. Besides DeltaF508, there are other point mutations, namely G542X, G551D, R553X, N1303K, and 621+1(G-->T), which are common among Caucasians. Additionally, a polyT polymorphism in intron 8 is also involved in the pathogenesis of CF. However, neither the prevalence nor the types of mutations causing CF in India are known. In this study, we aimed at estimating the frequency of the above common mutations and polymorphism in clinically suspected CF cases. We also carried out partial analysis of the CFTR gene, limited to exons 10 and 11, to identify other variations in these exons.

Methods: The multiplex amplification refractory mutation system (ARMS) test was applied for rapid simultaneous analysis of six most common CF mutations, in 100 normal and 39 elevated sweat chloride cases. The scanning of exons 10 and 11 was carried out by single-stranded conformation polymorphism/heteroduplex (SSCP/HD) analysis, followed by DNA sequencing in 50 normal and 37 elevated sweat chloride cases. A single ARMS-polymerase chain reaction assay was used to distinguish the 5T, 7T, and 9T alleles in 100 normal and 33 elevated sweat chloride cases.

Results: The multiplex ARMS analysis identified the DeltaF508 mutation at an allele frequency of 24% in Indian CF cases. However, the other predominant CF mutations were found to be absent. The 7T polyT variant was observed to be the most common allele, followed by the 9T, and 5T, which was the lowest. The DeltaF508 mutation was observed in all instances with the 9T variant. The SSCP/HD and DNA sequencing additionally revealed a known polymorphism (M470V, exon 10) and a known mutation [1525-1(G-->A), intron 9]. The 1525-1(G-->A) mutation, observed in a single 4-year-old male, is predicted to code for a class II defective CFTR protein.

Conclusion: The findings of this study suggest a difference in relative frequencies and spectrum of CFTR mutations in Indian CF cases. A larger screening study of the entire CFTR gene in clinically well defined CF cases is required to delineate common mutations in the CFTR gene and enable molecular diagnosis of CF in India.

Download full-text PDF

Source
http://dx.doi.org/10.1007/BF03260073DOI Listing

Publication Analysis

Top Keywords

cftr gene
16
deltaf508 mutation
12
common mutations
12
normal elevated
12
elevated sweat
12
sweat chloride
12
multiplex arms
8
sscp/hd analysis
8
molecular diagnosis
8
cystic fibrosis
8

Similar Publications

Novel Cystic Fibrosis Ferret Model Enables Visualization of CFTR Expression Cells and Genetic CFTR Reactivation.

Hum Gene Ther

January 2025

Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.

Cystic fibrosis (CF) is caused by mutations in the (). While gene therapy holds promise as a cure, the cell-type-specific heterogeneity of expression in the lung presents significant challenges. Current CF ferret models closely replicate the human disease phenotype but have limitations in studying functional complementation through cell-type-specific CFTR restoration.

View Article and Find Full Text PDF

Dry eye disease and morphological changes in the anterior chamber in people with cystic fibrosis.

J Cyst Fibros

January 2025

Pulmonology Department, Regional University Hospital of Malaga, Department of Medicine and Dermatology, University of Malaga, Biomedical Research Institute of Malaga (IBIMA) - Bionand Platform, Malaga, Spain. Electronic address:

Background: Cystic fibrosis (CF) is caused by variants in a gene that encodes a protein essential for water and ion transport in the epithelial cells of exocrine organs. Given the possible relationship of this protein and conjunctival and corneal epithelium, the aim of this study was to evaluate ophthalmologic alterations in people with CF.

Methods: Forty-five people with CF underwent pulmonary evaluation including inflammatory score (IS).

View Article and Find Full Text PDF

Reconsidering the Diagnosis: Abnormal Sweat Chloride Tests in Non-CF Bronchiectasis.

Pediatr Pulmonol

January 2025

Department of Internal Medicine, Division of Pulmonary and Critical Care, University of Virginia, Charlottesville, Virginia, USA.

Introduction: While the diagnosis of cystic fibrosis (CF) is often straightforward and reliant on correlation between genetic testing and clinical signs and symptoms, there is a subset where the distinction is not nearly as clearcut. This has previously been reported in patients identified through newborn screening but not meeting full CF diagnostic criteria, earning the label of CF Screen Positive, Inconclusive Diagnosis (CFSPID) instead. A homologous diagnostic category in adults is named CF Transmembrane Conductance Regulator-Related Disorder (CFTR-RD).

View Article and Find Full Text PDF

Limb-girdle muscular dystrophy type 2E/R4 (LGMD2E/R4) is a rare disease that currently has no cure. It is caused by defects in the gene, mainly missense mutations, which cause the impairment of the sarcoglycan complex, membrane fragility, and progressive muscle degeneration. Here, we studied the fate of some β-sarcoglycan (β-SG) missense mutants, confirming that, like α-SG missense mutants, they are targeted for degradation through the ubiquitin-proteasome system.

View Article and Find Full Text PDF
Article Synopsis
  • The study explores a new method for concentrating highly branched poly(β-amino ester) (HPAEs)/DNA nanoparticles for gene therapy aimed at treating cystic fibrosis, addressing challenges related to the high formulation concentrations required for clinical applications.
  • Researchers optimized a formulation using various buffers and achieved concentration through ultrafiltration, which significantly outperformed lyophilization by providing a 24-fold increase.
  • The concentrated formulation was effective in restoring CFTR protein production in lung epithelial cells, demonstrating better results than existing transfection reagents, highlighting its potential for future preclinical testing and clinical use.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!