Non-invasive first-trimester detection of paternal beta-globin gene mutations and polymorphisms as predictors of thalassemia risk at chorionic villous sampling.
OBJECTIVE
The objective was to evaluate the beta-globin gene mutations and polymorphisms in cell-free fetal DNA in the early first trimester (7-9th weeks' gestation) for the prediction of thalassemia risk at chorionic villous sampling (CVS).


METHODS
Beta-globin gene mutations and polymorphisms were analyzed in 97 carrier families and 100 control couples. Using conventional PCR-DGGE we carried out cell-free fetal DNA analysis in 37 couples in whom only the father was an IVSI-110 carrier.


RESULTS
Beta-globin gene mutations have 80% information content in contrast to 39% of polymorphisms. By non-invasive early first-trimester identification of the paternally transmitted IVSI-110 mutation, we reached a sensitivity and specificity of 96 and 100%, respectively. Although the detection rate of the Y chromosome in male fetuses was as high as 100%, beta-thalassemia allele drop-out cannot be excluded.


CONCLUSIONS
Even though there is high sensitivity in non-invasive paternally transmitted beta-thalassemia mutation detection, intense effort must be made to avoid misdiagnoses before the clinical application of this approach.
Lazaros
Leandros
L
Laboratory of Human Reproductive Genetics, Department of Obstetrics and Gynaecology, Medical School, University of Ioannina, Ioannina 45110, Greece.
Hatzi
Elizabeth
E
Bouba
Ioanna
I
Makrydimas
George
G
Dalkalitsis
Nicolaos
N
Stefos
Theodore
T
Paraskevaidis
Evangelos
E
Georgiou
Ioannis
I
D016022:Case-Control Studies; D015193:Chorionic Villi Sampling; D004252:DNA Mutational Analysis; D005260:Female; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000235:genetics*; D012680:Sensitivity and Specificity; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics*
D005914:Globins