Distribution of pathogenic variants in the CFTR gene in a representative cohort of people with cystic fibrosis in the Kingdom of Bahrain
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F24%3A10480428" target="_blank" >RIV/00064203:_____/24:10480428 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11130/24:10480428
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=iTPd.Y04Tr" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=iTPd.Y04Tr</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00438-024-02119-4" target="_blank" >10.1007/s00438-024-02119-4</a>
Alternative languages
Result language
angličtina
Original language name
Distribution of pathogenic variants in the CFTR gene in a representative cohort of people with cystic fibrosis in the Kingdom of Bahrain
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30101 - Human genetics
Result continuities
Project
<a href="/en/project/LM2018132" target="_blank" >LM2018132: The National Center for Medical Genomic</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecular Genetics and Genomics
ISSN
1617-4615
e-ISSN
1617-4623
Volume of the periodical
299
Issue of the periodical within the volume
1
Country of publishing house
DE - GERMANY
Number of pages
11
Pages from-to
52
UT code for WoS article
001222725400001
EID of the result in the Scopus database
2-s2.0-85193205886