CFTR Rearrangements in Spanish Cystic Fibrosis Patients: First New Duplication (35kb) Characterised in the Mediterranean Countries

María D. Ramos, Laia Masvidal, Javier Giménez, Eric Bieth, Manuela Seia, Marie des Georges, Lluís Armengol, Teresa Casals

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Developments in quantitative PCR technologies have greatly improved our ability to detect large genome rearrangements. In particular oligonucleotide-based array comparative genomic hybridisation has become a useful tool for appropriate and rapid detection of breakpoints. In this work, we have analysed 80 samples (42 unknown CF alleles) applying three quantitative technologies (MLPA, qPCR and array-CGH) to detect recurrent as well as novel large rearrangements in the Spanish CF population. Three deletions and one duplication have been identified in five alleles (12%). Interestingly, we provide the comprehensive characterisation of the first duplication in our CF cohort. The new CFTRdupProm-3 mutation spans 35.7 kb involving the 5′-end of the CFTR gene. Additionally, the RNA analysis has revealed a cryptic sequence with a premature termination codon leading to a disrupted protein. This duplication has been identified in five unrelated families from Spain, France and Italy with all patients showing the same associated haplotype, which is further evidence for its likely common Mediterranean origin. Overall, considering this and other previous studies, CFTR rearrangements account for 1.3% of the Spanish CF alleles.

Original languageEnglish
Pages (from-to)463-469
Number of pages7
JournalAnnals of Human Genetics
Volume74
Issue number5
DOIs
Publication statusPublished - Sep 2010

Fingerprint

Cystic Fibrosis
Alleles
Technology
Aptitude
Comparative Genomic Hybridization
Nonsense Codon
Oligonucleotide Array Sequence Analysis
Spain
Haplotypes
Italy
France
Genome
RNA
Polymerase Chain Reaction
Mutation
Population
Genes
Proteins

Keywords

  • CFTR
  • CFTR duplication
  • Cystic fibrosis
  • Genomic rearrangements
  • Mediterranean origin

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Medicine(all)

Cite this

CFTR Rearrangements in Spanish Cystic Fibrosis Patients : First New Duplication (35kb) Characterised in the Mediterranean Countries. / Ramos, María D.; Masvidal, Laia; Giménez, Javier; Bieth, Eric; Seia, Manuela; Georges, Marie des; Armengol, Lluís; Casals, Teresa.

In: Annals of Human Genetics, Vol. 74, No. 5, 09.2010, p. 463-469.

Research output: Contribution to journalArticle

Ramos, María D. ; Masvidal, Laia ; Giménez, Javier ; Bieth, Eric ; Seia, Manuela ; Georges, Marie des ; Armengol, Lluís ; Casals, Teresa. / CFTR Rearrangements in Spanish Cystic Fibrosis Patients : First New Duplication (35kb) Characterised in the Mediterranean Countries. In: Annals of Human Genetics. 2010 ; Vol. 74, No. 5. pp. 463-469.
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