Spectrum of cystic fibrosis mutations in Serbia and Montenegro and strategy for prenatal diagnosis.
We have screened 175 patients for molecular defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene using nondenaturing polyacrylamide gel electrophoresis (PAGE), denaturing gradient gel electrophoresis (DGGE), and sequencing. Six different mutations (F508del, G542X, 621+1G --> T, 2789+5G --> A, R1070Q, and S466X) accounted for 79.71% of CF alleles, with the F508del mutation showing a frequency of 72.28%. Another 12 mutations (R334W, 2184insA, I507del, 1525-1G --> A, E585X, R75X, M1I, 457TAT --> G, 574delA, 2723delTT, A120T, and 2907delTT) covered an additional 3.36%. A novel mutation (2723delTT) was found in one CF patient (F508del/2723delTT). Thus, a total of 18 mutations cover 82.57% of CF alleles. During our study, 72% of families at risk for having a CF child were found to be fully informative for prenatal diagnosis. Prenatal diagnosis was performed on 56 families; 76 analyses resulting in 16 affected, 38 carriers, and 22 healthy fetuses. These results imply that the molecular basis of CF in Serbia and Montenegro is highly heterogeneous, as is observed in other eastern and southern European populations. Because we detected more then 80% of CFTR alleles, results could be used for planning future screening and appropriate genetic counseling programs in our country.
Radivojevic
Danijela
D
Department of Medical Genetics, Mother and Child Health Institute of Serbia Dr. Vukan Cupic, Belgrade, Serbia and Montenegro. badane@beotel.yu
Djurisic
Marina
M
Lalic
Tanja
T
Guc-Scekic
Marija
M
Savic
Jovan
J
Minic
Predrag
P
Antoniadi
Thalia
T
Tzetis
Maria
M
Kanavakis
Emmanuel
E
D000483:Alleles; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005817:Genetic Counseling; D006801:Humans; D009154:Mutation / Q000235:genetics*; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012307:Risk Factors; D015022:Yugoslavia
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator