Distribution of CFTR Mutations in
Cystic Fibrosis Patients of Tunisian
Origin: Identification of Two Novel
Mutations

Messaoud, Taieb; Verlingue, C.; Denamur, Erick; Pascaud, Olivier; Quéré, Isabelle; Fattoum, S.; Élion, Jacques; Férec, Claude

doi:10.1159/000472165

Cited by 33 publications

(39 citation statements)

References 14 publications

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“…In our group of patients we found Δ508 present in frequency of 24% (36 of 150) which is consistent with certain regions like Turkey, Tunisia and Iran [24]. The frequency of Δ508 mutation in Turkish population is in complete agreement with population under study (24.5% Turkey versus 24% population under study) but in slight agreement with Iranian population (17.8% in Iran versus 24% ours population [17,25,26].…”

Section: Discussionsupporting

confidence: 86%

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Identification of Unique Pattern of CFTR Gene Mutations in Cystic Fibrosis in an Ethnic Kashmiri Population (North India)

Arshad¹,

ith²,

Sheikh³

et al. 2015

J Genet Syndr Gene Ther

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Background: Cystic Fibrosis (CF) one of the most common severe autosomal recessive disorders is caused by mutations in CFTR gene. The mutation distributions vary widely between different geographical and ethnic groups. In view of ethnic nature of Kashmiri population (North India), we aim at looking for the 3 common mutations Δ508, 3849+10 kb, C>T and W1282X in CF suspected cases. Method:The mutations were evaluated in 150 highly suspected children with CF, proven by clinical features. ARMS-PCR was used for mutation detection of Δ508 and W1282X while as 3849+10 kb, C>T was assessed by indigenously developed ARMS-PCR and results were confirmed by RFLP. Results:Of the 150 suspected CF cases, one of the three mutations was found in 60 out of the 300 alleles genotyped. Δ508 mutation was found in 36 of 150 (24%) cases, 3849+10 kb, C>T in 24 of 150(16%) cases while as no mutation was observed in W1282X. Interestingly 08 of 09 samples with normal sweat chloride were detected positive for 3849+10 kb, C>T mutation. Conclusion:In this report, frequency of the Δ508 mutation in Kashmiri children with CF is less as compared to the Western Countries. Interestingly, we identified 3849+10 kb, C>T mutation as unique in population under study with much higher frequency as compared to rest of the world. Further we found intron 19, 3849+10 kb, C>T mutation serves as marker in those CF cases having sweat chloride negative.

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Section: Discussionsupporting

confidence: 86%

“…This mutation frequency has been amplified to almost double that of the Δ508 mutation in this distinct population [24]. As with all other population specific mutations, the W1282X mutation is seen within the mutational arrays of the multitude of countries that have had a significant Ashkenazi Jewish influence.…”

Section: Introductionmentioning

confidence: 83%

Identification of Unique Pattern of CFTR Gene Mutations in Cystic Fibrosis in an Ethnic Kashmiri Population (North India)

Arshad¹,

ith²,

Sheikh³

et al. 2015

J Genet Syndr Gene Ther

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“…However its occurrence varies considerably between geographical locations and different populations with the lowest reported incidence in Tunisia (17.9%) and highest in Denmark (90%) (Messaoud et al, 1996;Schwartz et al, 1990). The spectrum of remaining CFTR mutations is highly variable and is represented by a large number of rare alleles.…”

Section: Mutations Within the Cftr Genementioning

confidence: 99%

Biochemical and Molecular Genetic Testing Used in the Diagnosis and Assessment of Cystic Fibrosis

McGrowder¹

2012

Cystic Fibrosis - Renewed Hopes Through Research

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“…According to the worldwide mutation survey conducted by the Cystic Fibrosis Genetic Analysis Consortium (CFGAC), the ⌬F508 allele accounted for 66% of 43,849 tested CF chromosomes (4). The occurrence of the ⌬F508 mutation varies considerably between different populations and geographical locations, with the lowest reported incidence in Tunisia (17.9%) (5) and the highest in Denmark (90%) (6). Most of the other CFTR mutations are rare, with only four mutations (G542X, N1303K, G551D, and W1282X) having overall frequencies above 1%.…”

Section: Clinical Relevancementioning

confidence: 99%

Prediction of Cellular Immune Responses against CFTR in Patients with Cystic Fibrosis after Gene Therapy

Figueredo

Limberis

Wilson

2007

Am J Respir Cell Mol Biol

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Different classes of mutations (class I-VI) of the cystic fibrosis (CF)transmembrane conductance regulator (CFTR) gene are responsible for lung/pancreatic disease. The most common mutation, ⌬F508, is characterized by expression of precursor forms of CFTR but no functional CFTR. Since only 5-10% of normal CFTR function is required to correct the electrophysiologic defect across the airway epithelium, gene therapy holds promise for treatment of patients with CF lung disease. However, efficient delivery and transgene expression are not the only parameters that may influence the success of gene therapy. Host-specific immune responses generated against the therapeutic CFTR protein may pose a problem, especially when the coding sequence between the normal CFTR and mutated CFTR differ. This phenomenon is more pertinent to class I mutations in which large fragments of the protein are not expressed. However, T cells directed against epitopes that span sequences containing class II-V mutations are also possible. We used MHC-binding prediction programs to predict the probability of cellular immune responses that may be generated against CFTR in ⌬F508 homozygote patients. Results obtained from running the prediction algorithms yielded a few high-scoring MHC-Class I binders within the specific sequences, suggesting that there is a possibility of the host to mount a cellular immune response against CFTR, even when the difference between therapeutic and host CFTR is a single amino acid (F) at position 508. Keywords: MHC ligand; CFTR; gene therapy; ⌬F508Cystic fibrosis (CF) is a debilitating human disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a protein that functions as a cAMP-regulated chloride channel. Defects of the CFTR protein result in abnormal chloride transport across the apical membranes of epithelial cells in the airways, pancreas, intestine, and vas deferens, leading to progressive lung disease, pancreatic dysfunction, elevated sweat electrolyte levels, and male infertility, respectively. More than 1,000 mutations have been identified in the CFTR gene. With reference to chloride transport dysfunction, CFTR mutations can be grouped into five classes that reflect the associated biosynthetic or functional alterations in the CFTR protein: (I) CFTR not synthesized, (II) defective processing, (III) defective regulation, (IV) defective conductance, and (V) partially defective production or processing. While for classes I (Received in original form August 23, 2006 and in final form November 17, 2006 ) Grants from the NIH (PO1-NL051746, P30-DK047757) (J.M.W.) and the CF Foundation supported this work.Correspondence and requests for reprints should be addressed to James M. Wilson, M.D., Ph.D

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Distribution of CFTR Mutations in Cystic Fibrosis Patients of Tunisian Origin: Identification of Two Novel Mutations

Cited by 33 publications

References 14 publications

Identification of Unique Pattern of CFTR Gene Mutations in Cystic Fibrosis in an Ethnic Kashmiri Population (North India)

Identification of Unique Pattern of CFTR Gene Mutations in Cystic Fibrosis in an Ethnic Kashmiri Population (North India)

Biochemical and Molecular Genetic Testing Used in the Diagnosis and Assessment of Cystic Fibrosis

Prediction of Cellular Immune Responses against CFTR in Patients with Cystic Fibrosis after Gene Therapy

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