Heterogeneity of the Cystic Fibrosis Phenotype in a Large Kindred Family in Qatar with Cystic Fibrosis Mutation (I1234V)

Wahab, Atqah Abdul; Thani, G. Al; Dawod, S. T.; Kambouris, Marios; Hamed, Moath

doi:10.1093/tropej/47.2.110a

Cited by 27 publications

(19 citation statements)

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“…Table 2 compares the frequency of mutations in the Lebanese population to those from neighboring Arab populations. In populations from Saudi Arabia, United Arab Emirates, Oman, Qatar, Kuwait, and Jordan the most commonly reported mutations were 1548delG, I123V, F508del, 3120 + 1G → A, and H139L; while F508del (7.4%-15%) and N1303K (1.5%-14%) are not common, and the mutation W1282X is absent from these populations ( Table 2) [1,3,[24][25][26]. In the Bahraini population, the most common mutations are 2043delG, 548A → T, 4041C → G, and F508del accounting for 66% of CF alleles [27].…”

Section: Discussionmentioning

confidence: 99%

Mutational spectrum of cystic fibrosis in the Lebanese population

Farra

Menassa

Awwad

et al. 2010

Journal of Cystic Fibrosis

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Section: Discussionmentioning

confidence: 99%

Mutational spectrum of cystic fibrosis in the Lebanese population

Farra

Menassa

Awwad

et al. 2010

Journal of Cystic Fibrosis

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“…Altogether, these results indicate that this CFTR unclassified variant (UV) should not cause CF. However, since the index patient had typical CF clinical features with only residual CFTR-mediated Cl − secretion in the colon and because other individuals homozygous for the same mutation had also been diagnosed as CF [41,42] we decided to further investigate the possible splicing consequences of c.3700A N G by analysing in silico the nucleotide sequence at the region where this mutation is located.…”

Section: Processing and Functional Analysis Of Pile1234val Cftr Mutantmentioning

confidence: 99%

Comparative ex vivo, in vitro and in silico analyses of a CFTR splicing mutation: Importance of functional studies to establish disease liability of mutations

Ramalho

Clarke

Sousa

et al. 2016

Journal of Cystic Fibrosis

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The Cystic Fibrosis p.Ile1234Val missense mutation actually creates a new dual splicing site possibly used either as a new acceptor or donor. Here, we aimed to test the accuracy of in silico predictions by comparing them with in vitro and ex vivo functional analyses of this mutation for an accurate CF diagnosis/prognosis. To this end, we applied a new in vitro strategy using a CFTR mini-gene which includes the complete CFTR coding sequence plus intron 22 (short version) which allows the assessment of alternatively spliced mRNA levels as well as the properties of the resulting abnormal CFTR protein regarding processing, intracellular localization and function. Our data demonstrate that p.Ile1234Val leads to usage of the alternative splicing donor (but not acceptor) resulting in alternative CFTR transcripts lacking 18 nts of exon 22 which produce a truncated CFTR protein with residual Cl- channel function. These results recapitulate data from native tissues of a CF patient. In conclusion, the existing in silico prediction models have limited application and ex vivo functional assessment of mutation effects should be made. Alternatively the in vitro strategy adopted here can be applied to assess the disease liability of mutations for an accurate CF diagnosis/prognosis.

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“…24 Information on genotypes in Asian patients with cystic fibrosis is limited to case reports or case series or data on migrant population in developed countries. [47][48][49][50][51][52][53][54][55][56][57][58] In view of small numbers it is difficult to reach to a conclusion, but available data suggest that mutation profile is very heterogeneous and frequency of F508del mutations is less than that seen in Caucasian population (Tables 2A-2C).…”

Section: Genotypesmentioning

confidence: 99%

Cystic fibrosis in India

Kabra

Lodha

et al. 2007

Pediatric Pulmonology

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Cystic fibrosis (CF) was considered to be non-existent in Indian subcontinent. Reports in last one decade have suggested that cystic fibrosis occurs in India but its precise magnitude is not known. Studies on migrant Indian population in United States and United Kingdom estimate frequency of CF as 1:10,000 to 1:40,000. The clinical features are similar to that reported in Caucasian population. CF in Indian children is usually diagnosed late and in advanced stage. Children are more malnourished and may have clinically evident deficiency of fat soluble vitamins. The frequency of clubbing, colonization with Pseudomonas, and laboratory evidence of pseudo-Bartter syndrome is relatively more at the time of diagnosis. Diagnostic facilities in form of sweat chloride estimation and genetic studies are not available readily. Mutation profile is different. The frequency of common mutation F508del in Indian children is between 19% and 34%. Other mutations are heterogeneous. Management of CF in India is difficult due to less number of trained manpower, limited availability, and high cost of pharmacologic agents. The determinants of early death include: severe malnutrition and colonization with Pseudomonas at the time of diagnosis, more than four episodes of lower respiratory infection per year and age of onset of symptoms before 2 months of age. To conclude, CF does occur in India; however, precise magnitude of problem is not known. There is need to create awareness amongst pediatricians, developing diagnostic facilities, and management protocols based on locally available resources.

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Heterogeneity of the Cystic Fibrosis Phenotype in a Large Kindred Family in Qatar with Cystic Fibrosis Mutation (I1234V)

Cited by 27 publications

References 0 publications

Mutational spectrum of cystic fibrosis in the Lebanese population

Mutational spectrum of cystic fibrosis in the Lebanese population

Comparative ex vivo, in vitro and in silico analyses of a CFTR splicing mutation: Importance of functional studies to establish disease liability of mutations

Cystic fibrosis in India

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