CFTR rearrangements in Spanish cystic fibrosis patients: first new duplication (35kb) characterised in the Mediterranean countries.
Ann Hum Genet
; 74(5): 463-9, 2010 Sep 01.
Article
in En
| MEDLINE
| ID: mdl-20560922
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA Mutational Analysis
/
Cystic Fibrosis Transmembrane Conductance Regulator
/
Cystic Fibrosis
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Humans
Country/Region as subject:
Europa
Language:
En
Journal:
Ann Hum Genet
Year:
2010
Type:
Article
Affiliation country:
Spain