Open AccessComprehensive genetic study of cystic fibrosis in Slovak patients in 25 years of genetic diagnostics
Author(s) -
Soltysova Andrea,
Tothova Tarova Eva,
Ficek Andrej,
Baldovic Marian,
Polakova Helena,
Kayserova Hana,
Kadasi Ludevit
Publication year - 2018
Publication title -
the clinical respiratory journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.789
H-Index - 33
eISSN - 1752-699X
pISSN - 1752-6981
DOI - 10.1111/crj.12651
Subject(s) - multiplex ligation dependent probe amplification , sanger sequencing , cystic fibrosis , medicine , mutation , genetics , genetic counseling , genetic testing , newborn screening , disease , population , gene mutation , gene , biology , pathology , pediatrics , environmental health , exon
Cystic fibrosis (CF) has one of the longest histories in hereditary disease molecular diagnostics. However, identification of causative mutations in the CFTR gene is complicated by over 2000 currently identified mutations; with more still being discovered. Knowledge of mutation spectrum may improve effective routine diagnostics and is obligatory in mutation‐specific treatment. Objectives This study presents comprehensive mutation screening of the CFTR gene; with 275 unrelated, clinically confirmed and treated cystic fibrosis (CF) patients diagnosed in 25 years genetic testing in Slovakia. Methods Detection of the most common CFTR mutations was performed by ELUCIGENE 29 and ELUCIGENE CF EU2 kits. HRM and dHPLC mutation screening methods with subsequent Sanger sequencing were applied for minor mutation screening, and MLPA analysis for deletion/duplication detection. Results A total of 70 different mutations were identified, from which the most common mutation F508del accounted for 60.36% of all disease alleles and 8 mutations have currently been observed only in Slovak patients. Two large deletions identified on chromosomes 2 and 22 were further characterized to identify breakpoints. Based on mutation screening results and neonatal screening we estimated incidence in Slovakian newborns at approximately 1:6000‐7000. Conclusion In our study, we identified mutations in 98.54% of all disease chromosomes, while 86.54% were identified using ELUCIGENE kits, 0.54% by MLPA analysis and 11.46% by sequencing analysis. Knowledge of the mutation spectrum in genetically diagnosed patients improves possibilities of genetic counseling and cascade screening in the affected families and Slovak population.