N1303K (c.3909C&gt;G) Mutation and Splicing: Implication of Its c.[744-33GATT(6); 869+11C&gt;T] Complex Allele in<i>CFTR</i>Exon 7 Aberrant Splicing

Farhat, Raed; Puissesseau, G.; El-Seedy, Ayman; Pasquet, Marie-Claude; Adolphe, Catherine; Corbani, Sandra; Mégarbané, André; Kitzis, Alain; Ladevèze, Véronique

doi:10.1155/2015/138103

Cited by 7 publications

(6 citation statements)

References 14 publications

(20 reference statements)

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“…He also presented with chronic diarrhoea and failure to thrive, without cholestasis (Table S1, Supplementary Information) . Among Lebanese patients, the c.3909C>G mutation is characterized by its severe pancreatic manifestation and by a variable pulmonary status (Tables , S1 (Supplementary Information)) . Six mutations in Jordan have been identified: c.296+19A>T, c.2279C>T, c.1013C>T, c.3670delA, c.4006delA and c.3731G>A (Table S1, Supplementary Information) .…”

Section: Resultsmentioning

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: Resultsmentioning

confidence: 99%

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

et al. 2018

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“… 15 - 17 Considered as a severe mutation, its phenotype is related to severe pancreatic consequences, and may lead to pancreatic insufficiency and diabetes mellitus. 15 , 16 , 18 Regarding pulmonary phenotype, the severity of the disease indicates great variability between the different mutations. 15 , 18 In this sample, patients identified with mutation N1303K in one of the alleles had pancreatic insufficiency.…”

Section: Discussionmentioning

confidence: 99%

“… 15 , 16 , 18 Regarding pulmonary phenotype, the severity of the disease indicates great variability between the different mutations. 15 , 18 In this sample, patients identified with mutation N1303K in one of the alleles had pancreatic insufficiency.…”

Section: Discussionmentioning

confidence: 99%

Genetic and phenotypic traits of children and adolescents with cystic fibrosis in Southern Brazil

et al. 2018

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Objectives: To characterize the main identified mutations on cystic fibrosis transmembrane conductance regulator (CFTR) in a group of children and adolescents at a cystic fibrosis center and its association with the clinical and laboratorial characteristics. Method: Descriptive cross-sectional study including patients with cystic fibrosis who had two alleles identified with CFTR mutation. Clinical, anthropometrical, laboratorial and pulmonary function (spirometry) data were collected from patients’ records in charts and described with the results of the sample genotyping. Results: 42 patients with cystic fibrosis were included in the study. The most frequent mutation was F508del, covering 60 alleles (71.4%). The second most common mutation was G542X (six alleles, 7.1%), followed by N1303K and R1162X mutations (both with four alleles each). Three patients (7.14%) presented type III and IV mutations, and 22 patients (52.38%) presented homozygous mutation for F508del. Thirty three patients (78.6%) suffered of pancreatic insufficiency, 26.2% presented meconium ileus, and 16.7%, nutritional deficit. Of the patients in the study, 59.52% would be potential candidates for the use of CFTR-modulating drugs. Conclusions: The mutations of CFTR identified more frequently were F508del and G542X. These are type II and I mutations, respectively. Along with type III, they present a more severe cystic fibrosis phenotype. More than half of the sample (52.38%) presented homozygous mutation for F508del, that is, patients who could be treated with Lumacaftor/Ivacaftor. Approximately 7% of the patients (7.14%) presented type III and IV mutations, therefore becoming candidates for the treatment with Ivacaftor.

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“…Previous reports in Bahrain indicated its frequency at 7.7% (Eskandarani 2002 ), whilst in Saudi Arabia, its frequency is between approximately 2–3% (Banjar et al 2020 ; el-Harith et al 1997 ). This mutation is considered as being an ‘Eastern Mediterranean’ mutation due to its highest worldwide frequency in Lebanon (27%), which might explain its presence in a case of Palestinian origin within our cohort (Farra et al 2010 ; Farhat et al 2015 ).…”

Section: Discussionmentioning

confidence: 86%

Distribution of pathogenic variants in the CFTR gene in a representative cohort of people with cystic fibrosis in the Kingdom of Bahrain

Majed,

Almoamen

et al. 2024

Mol Genet Genomics

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Background Cystic fibrosis (CF) is a rare multi-systemic recessive disorder. The spectrum and the frequencies of CFTR mutations causing CF vary amongst different populations in Europe and the Middle East. In this study, we characterised the distribution of CF-causing mutations (i.e. pathogenic variants in the CFTR gene) in a representative CF cohort from the Kingdom of Bahrain based on a three-decade-long analysis at a single tertiary centre. We aim to improve CF genetic diagnostics, introduce of CF neonatal screening and provide CFTR modulator therapy (CFTRm). Methods CFTR genotyping and associated clinical information were drawn from a longitudinal cohort. We sequenced 56 people with CF (pwCF) that had one or both CFTR mutations unidentified and carried out comprehensive bioinformatic- and family-based segregation analyses of detected variants, including genotype–phenotype correlations and disease incidence estimates. The study methodology could serve as a basis for other non-European CF populations with a high degree of consanguinity. Results Altogether 18 CF-causing mutations were identified, 15 of which were not previously detected in Bahrain, accounting for close to 100% of all population-specific alleles. The most common alleles comprise c.1911delG [2043delG; 22.8%], c.2988+1G > A [3120+1G>A; 16.3%], c.2989-1G>A [3121-1G>A; 14.1%], c.3909C>G [N1303K; 13.0%], and c.1521_1523delCTT [p.PheF508del; 7.6%]. Although the proportion of 1st cousin marriages has decreased to 50%, the frequency of homozygosity in our pwCF is 67.4%, thereby indicating that CF still occurs in large, often related, families. pwCF in Bahrain present with faltering growth, pancreatic insufficiency and classical sino-pulmonary manifestations. Interestingly, two pwCF also suffer from sickle cell disease. The estimated incidence of CF in Bahrain based on data from the last three decades is 1 in 9,880 live births. Conclusion The most commonCF-causing mutations in Bahraini pwCF were identified, enabling more precise diagnosis, introduction of two-tier neonatal screening and fostering administration of CFTRm.

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N1303K (c.3909C>G) Mutation and Splicing: Implication of Its c.[744-33GATT(6); 869+11C>T] Complex Allele inCFTRExon 7 Aberrant Splicing

Cited by 7 publications

References 14 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

Genetic and phenotypic traits of children and adolescents with cystic fibrosis in Southern Brazil

Distribution of pathogenic variants in the CFTR gene in a representative cohort of people with cystic fibrosis in the Kingdom of Bahrain

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