X chromosome dosage by quantitative fluorescent PCR and rapid prenatal diagnosis of sex chromosome aneuploidies.
During the past few years, rapid prenatal diagnosis of chromosome aneuploidies has been successfully achieved by quantitative fluorescent PCR (QF-PCR) amplification of chromosome-specific small tandem repeats (STR). This approach has proven to be very useful in clinical settings, since it allows the detection of major numerical disorders in a few hours after sampling. For the detection of Turner's syndrome (45,X), several highly polymorphic STR on the X chromosome are needed in order to reduce the likelihood that a normal female might be homozygous for all sequences and, consequently, that the test could fail to discriminate between samples retrieved from a Turner's and a normal female fetus. Here we report a new method for rapid and accurate detection of X chromosome copy number in prenatal samples that does not depend on STR heterozygosity. The test is based on QF-PCR amplification of the X-linked HPRT together with the autosomal D21S1411 used as internal control for quantification. In the course of this study, this assay allowed the prenatal diagnosis of a rare case of a normal female homozygous for four selected highly polymorphic X chromosome STR, as well as the assessment of the normal chromosome complement of a fetus homozygous for five chromosome 21 markers.
Cirigliano
Vincenzo
V
Departament de Genética Molecular, General Lab, Barcelona 08021, Spain. v_cirigliano@hotmail.com
Ejarque
Maijo
M
Fuster
Carme
C
Adinolfi
Matteo
M
D000649:Amniocentesis; D000782:Aneuploidy; D041321:Chromosomes, Human, X; D004303:Dosage Compensation, Genetic; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000235:genetics; D005453:Fluorescence; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008297:Male; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D012729:Sex Chromosome Aberrations; D025064:Sex Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics; D020080:Tandem Repeat Sequences; D014424:Turner Syndrome / Q000235:genetics
D005819:Genetic Markers; D007041:Hypoxanthine Phosphoribosyltransferase