Contribution of M470V variant to cystic fibrosis: First study in CF and normal Tunisian population

Nefzi, Malek; Fredj, Sondess Hadj; Tebib, Néji; Barsaoui, Sihem; Boussetta, Khédija; Siala, Hajer; Messaoud, Taieb

doi:10.1016/j.patbio.2015.07.004

Cited by 3 publications

(1 citation statement)

References 37 publications

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“…In most countries, the disease is diagnosed based on the clinical features of the patient and a sweat chloride test of 60 mmol/L or higher . However, some Arab countries have adopted the use of certain molecular diagnostic techniques for disease confirmation, including multiplex heteroduplex shift analysis, denaturing high‐pressure liquid phase chromatography (DHPLC), denaturing gradient gel electrophoresis (DGGE), and high‐resolution melting curve analysis, as well as sequencing techniques including Sanger sequencing and next‐generation sequencing …”

Section: Discussionmentioning

confidence: 99%

Spectrum of mutations of cystic fibrosis in the 22 Arab countries: A systematic review

et al. 2018

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Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, with various clinical manifestations that affect pulmonary, digestive, exocrine and male reproductive functions as well as the bones and kidneys. This study aimed to reveal the spectrum of CFTR gene mutations in Arab CF patients and their corresponding clinical phenotypes among the 22 Arab countries. We searched four literature databases (PubMed, Science Direct, Web of Science and Scopus) from their times of inception to January 2018. All possible search terms were used to encompass the different clinical phenotypes, disease incidences, CFTR mutations, ages and consanguinity rates of CF patients in the 22 Arab countries. Our search strategy identified 678 articles; of these, 72 were eligible for this systematic review. We retrieved data from 18 Arab countries; only 1766 Arab patients with CF were identified, even after additional searches using Google and Google Scholar. The search uncovered a wide spectrum of mutations, some of which are shared with other ethnic groups and some unique to Arab patients. Although the clinical phenotypes of Arab patients were typical of CF, several distinct phenotypes were reported. Despite the rarity of genetic epidemiological studies of CF patients among the 22 Arab nations, the disease is frequently reported in Arab countries where consanguineous marriage is common. Therefore, significant attention should be paid to this problem by implementing carrier and premarital screening, newborn screening and genetic counselling.

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Section: Discussionmentioning

confidence: 99%

Spectrum of mutations of cystic fibrosis in the 22 Arab countries: A systematic review

et al. 2018

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Association of M470V polymorphism of CFTR gene with variability of clinical expression of asthma: Case-report study

Wahabi

Fredj

Nefzi

et al. 2019

Allergologia et Immunopathologia

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Current Status of Genetic Diagnosis Laboratories and Frequency of Genetic Variants Associated with Cystic Fibrosis through a Newborn-Screening Program in Turkey

Bozdoğan

Mujde

Boğa

et al. 2021

Genes

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Background: Cystic fibrosis (CF) is the most common worldwide, life-shortening multisystem hereditary disease, with an autosomal recessive inheritance pattern caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The national newborn screening (NBS) program for CF has been initiated in Turkey since 2015. If the immunoreactive trypsinogen (IRT) is elevated (higher than 70 μg/L in the second control) and confirmed by sweat test or clinical findings, genetic testing is performed. The aims of this study are to emphasize the effect of NBS on the status of genetic diagnosis centers with the increasing numbers of molecular testing methods, and to determine the numbers and types of CFTR mutations in Turkey. Methods: The next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) results of 1595 newborns, who were referred to Cukurova University Adana Genetic Diseases Diagnosis and Treatment Center (AGENTEM) for molecular genetic testing, were evaluated with positive CF NBS program results since 2017. Results: According to the results; 560 (35.1%) of the 1595 patients carried at least 1 (one) CF-related variant, while 1035 patients (64.9%) had no mutation. Compound heterozygosity for two mutations was the most common in patients, while two detected variants were homozygote in 14 patients. A total of 161 variants were detected in 561 patients with mutations. Fifteen novel variants that have not been previously reported were found. Moreover, p.L997F was identified as the most frequent pathogenic mutation that might affect the IRT measurements used for the NBS. The distribution of mutation frequencies in our study showed a difference from those previously reported; for example, the well-known p.F508del was the third most common (n = 42 alleles), rather than the first. The most striking finding is that 313 cases had a pathogenic variant together with the V470M variant, which might have a cumulative effect on CF perpetuation. Conclusion: This study is the first to determine the mutational spectrum of CFTR in correlation with the NBS program in the Turkish population. NBS for CF raises issues regarding screening in diverse populations, both medical and non-medical benefits, and carrier identification. Through the lens of NBS, we focused on the integrated diagnostic algorithms and their effect on the results of genetic testing.

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Contribution of M470V variant to cystic fibrosis: First study in CF and normal Tunisian population

Cited by 3 publications

References 37 publications

Spectrum of mutations of cystic fibrosis in the 22 Arab countries: A systematic review

Spectrum of mutations of cystic fibrosis in the 22 Arab countries: A systematic review

Association of M470V polymorphism of CFTR gene with variability of clinical expression of asthma: Case-report study

Current Status of Genetic Diagnosis Laboratories and Frequency of Genetic Variants Associated with Cystic Fibrosis through a Newborn-Screening Program in Turkey

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