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CFTR Rearrangements in Spanish Cystic Fibrosis Patients: First New Duplication (35kb) Characterised in the Mediterranean Countries
Author(s) -
Ramos María D.,
Masvidal Laia,
Giménez Javier,
Bieth Eric,
Seia Manuela,
Georges Marie des,
Armengol Lluís,
Casals Teresa
Publication year - 2010
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.2010.00591.x
Subject(s) - gene duplication , genetics , biology , haplotype , multiplex ligation dependent probe amplification , allele , breakpoint , gene , genome , population , medicine , exon , chromosomal translocation , environmental health
Summary 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.