Clinical use of array comparative genomic hybridization (aCGH) for prenatal diagnosis in 300 cases.
OBJECTIVE
To evaluate the use of array comparative genomic hybridization (aCGH) for prenatal diagnosis, including assessment of variants of uncertain significance, and the ability to detect abnormalities not detected by karyotype, and vice versa.


METHODS
Women undergoing amniocentesis or chorionic villus sampling (CVS) for karyotype were offered aCGH analysis using a targeted microarray. Parental samples were obtained concurrently to exclude maternal cell contamination and determine if copy number variants (CNVs) were de novo, or inherited prior to issuing a report.


RESULTS
We analyzed 300 samples, most were amniotic fluid (82%) and CVS (17%). The most common indications were advanced maternal age (N=123) and abnormal ultrasound findings (N=84). We detected 58 CNVs (19.3%). Of these, 40 (13.3%) were interpreted as likely benign, 15 (5.0%) were of defined pathological significance, while 3 (1.0%) were of uncertain clinical significance. For seven (approximately 2.3% or 1/43), aCGH contributed important new information. For two of these (1% or approximately 1/150), the abnormality would not have been detected without aCGH analysis.


CONCLUSIONS
Although aCGH-detected benign inherited variants in 13.3% of cases, these did not present major counseling difficulties, and the procedure is an improved diagnostic tool for prenatal detection of chromosomal abnormalities.
Van den Veyver
Ignatia B
IB
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
Patel
Ankita
A
Shaw
Chad A
CA
Pursley
Amber N
AN
Kang
Sung-Hae L
SH
Simovich
Marcia J
MJ
Ward
Patricia A
PA
Darilek
Sandra
S
Johnson
Anthony
A
Neill
Sarah E
SE
Bi
Weimin
W
White
Lisa D
LD
Eng
Christine M
CM
Lupski
James R
JR
Cheung
Sau Wai
SW
Beaudet
Arthur L
AL
D000328:Adult; D000649:Amniocentesis; D015193:Chorionic Villi Sampling; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D005817:Genetic Counseling; D006801:Humans; D007621:Karyotyping; D046228:Microarray Analysis; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*