Rapid aneuploidy diagnosis by array comparative genomic hybridization using uncultured amniocytes in a pregnancy with fetal nuchal edema and mild ascites

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RESEARCH LETTER

Rapid Aneuploidy Diagnosis by Array Comparative

Genomic Hybridization Using Uncultured

Amniocytes in a Pregnancy With Fetal Nuchal Edema

and Mild Ascites

Chih-Ping Chen

1,2,3,4,5,6

*

, Yi-Ning Su

7

, Pei-Chen Wu

1

, Chen-Chi Lee

1

,

Chen-Wen Pan

1

, Wayseen Wang

2,8

1_{Department of Obstetrics and Gynecology, Mackay Memorial Hospital,}2_{Department of Medical Research, Mackay Memorial} Hospital, Taipei, Taiwan,3Department of Biotechnology, Asia University,4School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan,5_{Institute of Clinical and Community Health Nursing, National} Yang-Ming University,6Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University,7Department of Medical Genetics, National Taiwan University Hospital, and 8_{Department of Bioengineering, Tatung University, Taipei,} Taiwan.

Received May 13, 2011; accepted May 19, 2011 Available online July 7, 2011

A 37-year-old, Gravida 2 Para 0, woman was referred for genetic counseling at 14 weeks of gestation because of an increased nuchal thickness (Fig. 1). Prenatal ultrasound at 16 weeks of gestation showed nuchal edema and mild fetal ascites (Fig. 2). Amniocentesis was performed, and 28 mL amniotic fluid was aspired, of which 16 mL of amni-otic fluid was applied for array comparative genomic hybridization (aCGH) using uncultured amniocytes, and 10 mL was applied for conventional cytogenetic analysis using cultured amniocytes. Within 1 week,

oligonucleotide-based aCGH analysis using Oligo HD Scan (CMDX, Irvine, CA, USA) showed the result of trisomy 21 (arr cgh 21q11.2q22.3 [13,339,394-46,944,323]3) (Fig. 3). Conventional cytoge-netic analysis later revealed a karyotype of 47,XY,þ21 (Fig. 4). The pregnancy was terminated at 18 weeks of gestation, and a 226-g edematous fetus was delivered.

Bacterial artificial chromosome (BAC)-based aCGH and oligonucleotide-based aCGH have been successfully applied for rapid aneuploidy diagnosis (RAD) of both partial aneu-ploidy[1]and full aneuploidy[2]. RAD refers to the appli-cations of interphase fluorescence in situ hybridization, quantitative fluorescent polymerase chain reaction, multi-plex ligation-dependent probe amplification, and aCGH for rapid prenatal diagnosis of aneuploidies[3]. The aCGH has the advantage of achieving a rapid genome-wide analysis without the need for cell culture. It has been shown that

* Address correspondence to: Dr. Chih-Ping Chen, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, 92, Section 2, Chung-Shan North Road, Taipei, Taiwan. E-mail: [email protected](C.-P. Chen).

a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m

j o u r n a l h o m e p a g e : w w w . j m u - o n l i n e . c o m Journal of Medical Ultrasound (2011) 19, 64_e67

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the results of aCGH can be available within an average of 6 days for uncultured cells[4]. However, aCGH has difficulty in detecting low-level mosaicism, balanced translocation, inversion, and polyploidy[5].

The present case was associated with Down syndrome, nuchal edema, and mild fetal ascites. Snijders et al [6]

found that nuchal edema was diagnosed in 38% of fetuses with trisomy 21. About one-third of the fetuses with nuchal edema have chromosome abnormalities, mainly trisomies 21, 18, and 13 [7]. Snijders et al [6] found that hydrops

fetalis was diagnosed in 20% of the fetuses with trisomy 21 (nZ 155). Jauniaux et al [8] reported chromosome abnormalities in 15.7% (94/600) of the fetuses with nonimmune hydrops fetalis, and about 38.3% (36/94) of the aneuploid hydropic fetuses were diagnosed with trisomy 21.

In conclusion, prenatal diagnosis of fetal nuchal edema with mild ascites should alert one to the possibility of chromosomal abnormalities, and aCGH has the advantage of RAD.

Fig. 2. Prenatal ultrasound at 16 weeks of gestation shows (A) nuchal edema (arrow) and (B) mild fetal ascites (arrow). Fig. 1. Prenatal ultrasound at 14 weeks of gestation shows an increased nuchal thickness of 9.3 mm (arrow).

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Acknowledgments

This work was supported by research grants NSC-97-2314-B-195-006-MY3 and NSC-99-2628-B-195-001-MY3 from the National Science Council and MMH-E-100-04 from Mackay Memorial Hospital, Taipei, Taiwan.

References

[1] Chen C-P, Su Y-N, Tsai F-J, et al. Terminal 2q deletion and distal 15q duplication: prenatal diagnosis by array comparative genomic hybridization using uncultured amniocytes. Taiwan J Obstet Gynecol 2009;48:441e5.

[2] Chen C-P, Su Y-N, Lin S-Y, et al. Rapid aneuploidy diagnosis by multiplex ligation-dependent probe amplification and array comparative genomic hybridization in pregnancy with major congenital malformations. Taiwan J Obstet Gynecol 2011;50: 85_e94.

[3] Bui TH. Prenatal cytogenetic diagnosis: gone FISHing, BAC soon! Ultrasound Obstet Gynecol 2007;30:247_e51.

[4] Sahoo T, Cheung SW, Ward P, et al. Prenatal diagnosis of chromosomal abnormalities using array-based comparative genomic hybridization. Genet Med 2006;8: 719e27.

[5] Chen C-P, Lin H-M, Su Y-N, et al. Mosaic trisomy 9 at amnio-centesis: prenatal diagnosis and molecular genetic analyses. Taiwan J Obstet Gynecol 2010;49:341e50.

Fig. 4. Conventional cytogenetic analysis using cultured amniocytes shows a karyotype of 47,XY,þ21.

Fig. 3. Oligonucleotide-based array comparative genomic hybridization analysis using uncultured amniocytes shows a duplica-tion of chromosome 21 (arrow) consistent with the diagnosis of trisomy 21.

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[6] Snijders RJM, Farrias M, von Kaisenberg C, et al. Fetal abnormalities. In: Snijders RJM, Nicolaides KH, editors. Ultrasound markers for fetal chromosomal defects. New York: Parthenon Publishing Group; 1996. p. 1e62.

[7] Chen C-P. Prenatal sonographic features of fetuses in trisomy 13 pregnancies (III). Taiwan J Obstet Gynecol 2009;48:342e9. [8] Jauniaux E, Van Maldergem L, De Munter C, et al. Nonimmune

hydrops fetalis associated with genetic abnormalities. Obstet Gynecol 1990;75:568e72.