title: Microarray comparative genomic hybridization (CGH)-based prenatal diagnosis for chromosome abnormalities using cell-free fetal DNA in amniotic fluid.
abstract: Cell-free fetal DNA (cffDNA) in the supernatant of amniotic fluid, which is usually discarded, can be used as a sample for prenatal diagnosis. For rapid prenatal diagnosis of frequent chromosome abnormalities, for example trisomies 13, 18, and 21, and monosomy X, using cffDNA, we have developed a targeted microarray-based comparative genomic hybridization (CGH) panel on which BAC clones from chromosomes 13, 18, 21, X, and Y were spotted. Microarray-CGH analysis was performed for a total of 13 fetuses with congenital anomalies using cffDNA from their uncultured amniotic fluid. Microarray CGH with cffDNA led to successful molecular karyotyping for 12 of 13 fetuses within 5 days. Karyotypes of the 12 fetuses (one case of trisomy 13, two of trisomy 18, two of trisomy 21, one of monosomy X, and six of normal karyotype) were later confirmed by conventional chromosome analysis using cultured amniocytes. The one fetus whose molecular-karyotype was indicated as normal by microarray CGH actually had a balanced translocation, 45,XY,der(14;21)(q10;q10). The results indicated that microarray CGH with cffDNA is a useful rapid prenatal diagnostic method at late gestation for chromosome abnormalities with copy-number changes, especially when combined with conventional karyotyping of cultured amniocytes.
authors.affiliation: Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, 852-8501, Nagasaki, Japan.|Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Miura
authors.affiliation: Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, 852-8501, Nagasaki, Japan. kiyonori@net.nagasaki-u.ac.jp.
authors.forename: Kiyonori
authors.initials: K
authors.lastname: Miura
authors.affiliation: Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, 852-8501, Nagasaki, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Masuzaki
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Koh-Ichiro
authors.initials: KI
authors.lastname: Yoshiura
authors.affiliation: The Research Institute of Personalized Health Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan.
authors.forename: Nadiya
authors.initials: N
authors.lastname: Sosonkina
authors.affiliation: Kyushu Medical Science, Nagasaki, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Harada
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|Kyushu Medical Science, Nagasaki, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Shimokawa
authors.affiliation: Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, 852-8501, Nagasaki, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakayama
authors.affiliation: Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, 852-8501, Nagasaki, Japan.
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Yoshimura
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.|SORST, Japan Science and Technology Agency (JST), Kawaguchi, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|SORST, Japan Science and Technology Agency (JST), Kawaguchi, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Niikawa
authors.affiliation: Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, 852-8501, Nagasaki, Japan.|Department of Obstetrics and Gynecology, Sasebo Chuo Hospital, Nagasaki, Japan.
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Ishimaru
mesh_terms: D000653:Amniotic Fluid / Q000737:chemistry* / Q000166:cytology; D002474:Cell-Free System; D002869:Chromosome Aberrations; D004247:DNA / Q000032:analysis* / Q000378:metabolism; D005333:Fetus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007621:Karyotyping; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011296:Prenatal Diagnosis / Q000379:methods*
chemical_list: D004247:DNA