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Distribution of pathogenic variants in the CFTR gene in a representative cohort of people with cystic fibrosis in the Kingdom of Bahrain.
Majed, Osama A Karim; Majed, Fatema Osama; Almoamen, Nabeel Jasim; Alsatrawi, Husain Baqer; Shehabi, Salma Dawood; Hrbková, Jana; Libik, Malgorzata; Macek, Milan.
Affiliation
  • Majed OAK; Salmaniya Medical Complex, Rd. No. 2904, Manama, Kingdom of Bahrain. osama_ka@hotmail.com.
  • Majed FO; Royal University of Surgeons in Ireland, Medical University of Bahrain, Al Sayh Muharraq Governorate, Busaiteen, Kingdom of Bahrain. osama_ka@hotmail.com.
  • Almoamen NJ; Royal University of Surgeons in Ireland, Medical University of Bahrain, Al Sayh Muharraq Governorate, Busaiteen, Kingdom of Bahrain.
  • Alsatrawi HB; Salmaniya Medical Complex, Rd. No. 2904, Manama, Kingdom of Bahrain.
  • Shehabi SD; Salmaniya Medical Complex, Rd. No. 2904, Manama, Kingdom of Bahrain.
  • Hrbková J; Department of Pediatrics, University Hospital in Coventry and Warwickshire, Coventry, United Kingdom.
  • Libik M; Department of Biology and Medical Genetics, 2nd Faculty of Medicine and Motol University Hospital, Charles University, Prague, Czechia.
  • Macek M; Department of Biology and Medical Genetics, 2nd Faculty of Medicine and Motol University Hospital, Charles University, Prague, Czechia.
Mol Genet Genomics ; 299(1): 52, 2024 May 14.
Article in En | MEDLINE | ID: mdl-38744777
ABSTRACT

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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cystic Fibrosis Transmembrane Conductance Regulator / Cystic Fibrosis / Mutation Limits: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male / Newborn Country/Region as subject: Asia Language: En Journal: Mol Genet Genomics Journal subject: BIOLOGIA MOLECULAR / GENETICA Year: 2024 Type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cystic Fibrosis Transmembrane Conductance Regulator / Cystic Fibrosis / Mutation Limits: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male / Newborn Country/Region as subject: Asia Language: En Journal: Mol Genet Genomics Journal subject: BIOLOGIA MOLECULAR / GENETICA Year: 2024 Type: Article