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Partial Trisomy View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector ■ CASE REPORT ■ PARTIAL TRISOMY 16P (16P12.2PTER) AND PARTIAL MONOSOMY 22Q (22Q13.31QTER) PRESENTING WITH FETAL ASCITES AND VENTRICULOMEGALY: PRENATAL DIAGNOSIS AND ARRAY COMPARATIVE GENOMIC HYBRIDIZATION CHARACTERIZATION Chih-Ping Chen1,2,3,4,5,6*, Yi-Ning Su7, Richard Shih-Hung Young8, Fuu-Jen Tsai4,9, Pei-Chen Wu1, Schu-Rern Chern2, Dai-Dyi Town1, Chen-Wen Pan1, Wayseen Wang2,10 Departments of 1Obstetrics and Gynecology and 2Medical Research, Mackay Memorial Hospital, 5Institute of Clinical and Community Health Nursing, 6Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, 7Department of Medical Genetics, National Taiwan University Hospital, and 10Department of Bioengineering, Tatung University, Taipei; 3Department of Biotechnology, Asia University, 4School of Chinese Medicine, College of Chinese Medicine, China Medical University, and 9Departments of Medical Genetics and Medical Research, China Medical University Hospital, Taichung; 8Department of Obstetrics and Gynecology, Hung-Chi Women and Children’s Hospital, Jhung-Li, Taiwan. SUMMARY Objective: To present prenatal diagnosis and array comparative genomic hybridization (aCGH) characterization of partial trisomy 16p (16p12.2pter) and partial monosomy 22q (22q13.31qter) presenting with fetal ascites and ventriculomegaly in the second trimester. Case Report: A 31-year-old woman, gravida 2, para 1, was referred to the hospital at 20 weeks of gestation because of fetal ascites. Amniocentesis revealed a derivative chromosome 22. Subsequent parental karyotyping revealed that the father carried a balanced reciprocal translocation between 16p12 and 22q13. Bacterial artificial chromosome-based aCGH using amniocyte DNA demonstrated partial trisomy 16p and partial monosomy 22q [arr cgh 16p13.3p12.2 (CTD-3077J14RP11-650D5)×3, 22q13.31q13.33 (RP1-111J24CTD-3035C16)×1]. Oligonucleotide-based aCGH showed a 20.9-Mb duplication of distal 16p and an approximate 3.7-Mb deletion of distal 22q. Level II ultrasound revealed fetal ascites and ventriculomegaly. The pregnancy was terminated and a malformed male fetus was delivered with craniofacial dysmorphism and abnormalities of the digits. The fetal karyotype was 46,XY,der(22)t(16;22)(p12.2;q13.31)pat. The paternal karyotype was 46,XY,t(16;22)(p12.2;q13.31). Conclusion: Partial trisomy 16p can be associated with fetal ascites and ventriculomegaly in the second trimester. Prenatal sonographic detection of fetal ascites in association with ventriculomegaly should alert chromosomal abnormalities and prompt cytogenetic investigation, which may lead to the identification of an unexpected parental translocation involving chromosomal segments associated with cerebral and vascular abnormalities. [Taiwan J Obstet Gynecol 2010;49(4):506–512] Key Words: chromosome 16, chromosome 22, fetal ascites, monosomy 22q, trisomy 16p, ventriculomegaly *Correspondence to: Dr Chih-Ping Chen, Department Introduction of Obstetrics and Gynecology, Mackay Memorial Hospital, 92, Section 2, Chung-Shan North Road, Partial trisomy 16p is a rare clinical recognizable syn- Taipei, Taiwan. E-mail: [email protected] drome characterized by mental retardation, growth Accepted: April 28, 2010 retardation, craniofacial abnormalities, abnormally 506 Taiwan J Obstet Gynecol • December 2010 • Vol 49 • No 4 Partial Trisomy 16p and Partial Monosomy 22q placed thumbs, finger tapering, simian crease, club The parents were non-consanguineous and healthy and hand/foot, hammer toes, urogenital abnormalities, car- there was no family history of congenital malformations. diac anomalies, respiratory distress, pulmonary vascu- Prenatal sonography at 20 gestational weeks revealed lar diseases and other vascular anomalies [1–11]. The a male fetus with fetal biometry equivalent to 20 weeks, 22q13.3 deletion syndrome or Phelan-McDermid syn- a normal amount of amniotic fluid and fetal ascites. drome (OMIM 606232) is characterized by large or The internal organs were unremarkable. Amniocente- unusual ears, relatively large hands, full brow, dolicho- sis revealed a derivative chromosome 22, or der(22) cephaly, ptosis, full cheeks, a bulbous nose, a pointed (Figure 1). Subsequent parental karyotyping revealed chin, autistic behavior, neonatal hypotonia, global dev- that the father carried a balanced reciprocal transloca- elopmental delay, normal or accelerated growth and tion between 16p12 and 22q13 (Figure 2). The karyo- absent to severely delayed speech [12–16]. A concomi- type of the mother and her daughter were normal. tant occurrence of partial trisomy 16p and 22q13.3 Bacterial artificial chromosome-based aCGH of amnio- deletion is unusual. We previously described the appli- cyte DNA using CMDX bacterial artificial chromosome- cation of array comparative genomic hybridization based aCGH CA3000 chips (CMDX, Irvine, CA, USA) (aCGH) in prenatal diagnosis of aneuploidy [17,18]. demonstrated partial trisomy 16p and partial monosomy Here, we report prenatal diagnosis and aCGH charac- 22q [arr cgh 16p13.3p12.2 (CTD-3077J14RP11- terization of partial trisomy 16p (16p12.2pter) and 650D5)×3, 22q13.31q13.33 (RP1-111J24CTD- partial monosomy 22q (22q13.31qter) in a fetus 3035C16)×1] (Figure 3). Oligonucleotide-based aCGH associated with fetal ascites and ventriculomegaly. using Oligo HD Scan (CMDX, Irvine, CA, USA) showed a 20.9-Mb duplication of distal 16p and an approxi- mate 3.7-Mb deletion of distal 22q (Figure 4). Level II Case Report ultrasound revealed fetal ascites and ventriculomegaly (Figure 5). The pregnancy was terminated at 22 gesta- A 31-year-old woman, gravida 2, para 1, was referred tional weeks. A 436-g male fetus was delivered with dys- to the hospital at 20 weeks of gestation because of morphic features including a round face, hypertelorism, fetal ascites which had developed 2 weeks prior to prominent glabella, a bulbous nose, a depressed nasal referral. She had a 5-year-old, healthy daughter. The bridge, full cheeks, anteverted nares, a long philtrum, woman reported no teratogenic medications, recent thin lips, micrognathia, low-set ears, a short neck, finger viral infections, diabetes mellitus or hypertension. The tapering, malposition of the toes, flexion-deformity of maternal blood group was O, Rh-positive and the the fingers, bilateral proximally inserted thumbs, a maternal syphilis screen was negative but thalassemia bilateral simian crease, a gap between the first and the screen was positive. The paternal thalassemia screen second toes, and overlapping fingers (Figures 6 and 7). was negative. Maternal rubella IgG levels were consistent The external genitalia and anus were normal. Molecular with past history of a childhood infection of rubella. analysis revealed negative findings for parvovirus B19, Figure 1. G-banded karyotype of the fetus shows a derivative chromosome 22, or der(22). The karyotype is 46,XY,der(22) t(16;22)(p12.2;q13.31)pat. The arrows indicate the breakpoints on normal chromosomes. Taiwan J Obstet Gynecol • December 2010 • Vol 49 • No 4 507 C.P. Chen, et al Figure 2. G-banded karyotype of the father shows a der(16) and a der(22). The karyotype is 46,XY,t(16;22)(p12.2;q13.31). The arrows indicate the breakpoints on normal chromosomes. Chromosome 16 Chromosome 22 0 0 p13.3 p13 p13.2 10 p12 5 p13.13 p13.12 p13.11 p11.2 p12.3 10 20 p11.1 p12.2 p12.1 p11.1 15 p11.2 30 q11.21 p11.1 20 q11.22 q11.1 40 q11.23 q11.2 25 q12.1 q12.1 50 q12.2 q12.2 30 q13 q12.3 q21 60 35 q22.1 q13.1 q22.2 70 q22.3 40 q13.2 q23.1 q23.2 80 q13.31 45 q23.3 q24.1 q13.32 q24.2 q13.33 q24.3 50 .22 .33 .567 1 1.52 34.5 .22 .33 .567 1 1.52 34.5 Ratio Ratio Figure 3. Bacterial artificial chromosome-based array comparative genomic hybridization shows partial trisomy 16p [arr cgh 16p13.3p12.2 (CTD-3077J14RP11-605D5)×3] and partial monosomy 22q [arr cgh 22q13.31q13.33 (RP1-111J24 CTD-3035C16)×1]. cytomegalovirus, toxoplasma and herpes simplex virus Discussion in the cord blood. The karyotype of the father was 46,XY,t(16;22)(p12.2;q13.31). The karyotype of the The present case manifested characteristic craniofacial fetus was 46,XY,der(22)t(16;22)(p12.2;q13.31)pat. and limb abnormalities associated with partial trisomy 508 Taiwan J Obstet Gynecol • December 2010 • Vol 49 • No 4 Taiwan JObstetGynecol Taiwan A Chromosome 16 B Chromosome 22 p13.3 p13.2 p12.1 p11.2 q12.1 q21 q22.1 q23.1 q11.21 q12.1 q12.2 q12.3 q13.1 q13.2 q13.31 Genes Genes Exons Exons CNVs CNVs miRNA miRNA hsa-mir-1826 hsa-mir-138-2 hsa-mir-1910 Agilent105KV6 Agilent105KV6 • Agilent180K Agilent180K December 2010 Illumina_CytoSNP-12v Illumina_CytoSNP-12v Illumina_Omni1-Quad Illumina_Omni1-Quad 2.5 2.5 2.0 2.0 1.5 1.5 1.0 • 1.0 Vol 49 Vol 0.5 0.5 0 0 • − −0.5 No 4 0.5 − −1.0 1.0 − −1.5 1.5 −2.0 −2.0 − −2.5 2.5 0 10 Mb 20 Mb 30 Mb 40 Mb 50 Mb 60 Mb 70 Mb 80 Mb 0 5 Mb 10 Mb 15 Mb 20 Mb 25 Mb 30 Mb 35 Mb 40 Mb 45 Mb Chromosome 16 Chromosome 22 q13.31 q13.32 q13.33 p13.3 p13.2 p13.13 p13.12 p13.11 p12.3 p12.1 Genes FAM19A5 Genes A2BP1 Exons Exons CNVs CNVs miRNA hsa-mir-1249 miRNA hsa-mir-548h-2 Agilent105KV6 Agilent105KV6 Agilent180K Agilent180K Illumina_CytoSNP-12v Illumina_CytoSNP-12v Illumina_Omni1-Quad Illumina_Omni1-Quad 22q Monosomy 16pandPartial Trisomy Partial 2.5 2.5 2.0 2.0 1.5 1.5 1.0 1.0 0.5 0.5 0 0 −0.5 −0.5 −1.0 −1.0 −1.5 −1.5 −2.0 −2.0 − −2.5 2.5 0 5 Mb 10 Mb 15 Mb 20 Mb 25 Mb 43 Mb 44 Mb 45 Mb 46 Mb 47 Mb 48 Mb 49 Mb 50 Mb Figure 4.
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