Prenatal detection of an inverted duplication deletion in the long arm of chromosome 1 in a fetus with increased nuchal translucency. Molecular cytogenetic analysis and review of the literature Emmanouil Manolakos a,j , Stavros Sifakis f , Sotirios Sotiriou g , Panagiotis Peitsidis b , Makarios Eleftheriades c , Vassilis Mersinias a , Thomas Liehr i , Loretta Thomaidis d , George Kitsos e , Ioannis Papoulidis a , Michael B. Petersen h and Sandro Orru j Clinical Dysmorphology 2012, 21:101–105 a Laboratory of Cytogenetics Eurogenetica, b Department of Obstetrics and Gynaecology ‘Helena Venizelou’ Hospital, c EmbryoCare, Fetal Medicine Centre, d Department of Pediatrics, University of Athens, ‘Aglaia Kyriakou’ Children’s Hospital, e Department of Opthalmology, Ioannina University Hospital, f Depart- ment of Obstetrics and Gynecology, University Hospital of Heraklion, Crete, g Department of Embryology, University of Thessaly, Larissa, h Department of Genetics Institute of Child Health, Aghia Sophia Hospital, Athens, Greece, i Institute of Human Genetics and Anthropology, Friedrich-Schiller-University, Jena, Germany and j Department of Medical Genetics, University of Cagliari, Binaghi Hospital, Cagliari, Italy Correspondence to Dr Panagiotis Peitsidis, MD, PhD, Department of Obstetrics and Gynaecology ‘Helena Venizelou’ Hospital, Proussis 22 p.c:17123, Athens, Greece Tel:+30 697 222 1553; fax: +30 210 74 74 908; e-mail: panagiotis_pp@yahoo.com Received 22 February 2011 Accepted 26 October 2011 List of key features Hydrops fetalis Increased nuchal translucency Oligamnios Introduction Partial trisomy 1q syndrome is a rare chromosomal aberration. Most cases arise from de-novo unbalanced translocations or from pure partial duplications of chromosome 1q, mostly involving the 1q31.2–q43 region (Watson et al., 1990; Bartsch et al., 2001; Kı ´mya et al., 2002; Nowaczyk et al., 2003; Machlitt et al., 2005; Utine et al., 2007; Wax et al., 2008). On the basis of the orientation of the duplicated segment, they can be divided into direct and inverted duplications. Inverted duplications are cytogenetic rearrangements due to meiotic errors during homologous chromosome pairing and are usually associated with the deletion of the contiguous distal region (Bonaglia et al., 2000). Only four postnatal cases have been described as inverted duplica- tions 1q, two of which were associated with terminal deletions (Mewar et al., 1994; De Brasi et al., 2001; Poli- tyko et al., 2005; Balasubramanian et al., 2009). We report the first prenatally diagnosed case of trisomy 1q31.2–q43 due to an inverted duplication of this region, associated with a terminal deletion of the long arm of the rearranged chromosome 1. Clinical report A 33-year-old female, gravida 1, was referred for further prenatal diagnosis because of fetal ultrasound examina- tion at 12 weeks of gestation that showed increased nuchal translucency (NT) 5.8 mm (Fig. 1), with a calculated Down syndrome risk of 1/43. The family history was unremarkable. Chromosome analysis was performed according to standard procedures with Giemsa-banded chromosomes from cul- tured chorionic villi (CVS), and fetal DNA was extracted directly using the Instagene Matrix resin (Bio-Rad Laboratories, Hercules, California, USA). A multiplex quantitative fluorescent PCR (QF-PCR) analysis was performed. The QF-PCR analysis was carried out using 10 ng fetal DNA extracted from CVS. The QF-PCR products were analyzed by capillary electrophoresis on an ABI 3130 automated (Applied Biosystems, Foster City, California, USA) DNA sequencer. All short tandem repeat markers for chromosomes 13, 18, 21, and X were observed in a normal diallelic pattern. The cytogenetic analysis showed a 46,XY,der(1) karyotype. Subsequent chromo- some analysis of lymphocyte cultures of both parents was performed and appeared normal. After genetic counseling, the parents decided to terminate the pregnancy. The CVS cultures were subjected to fluorescence in–situ hybridization for further confirmation of the diagnosis. The aberrant chromosome 1 was characterized by fluorescence in-situ hybridization using multicolor banding for chromo- some 1 (10 pcp), multicolor banding probes, as described previously. The chromosomal rearrangement was molecular cytogenetically unbalanced, as the subtelomere probe (Abbott Vysis; Abbott Laboratories, Illinois, USA) was not present in the 1qter (data not shown). The karyotype was identified as 46,XY,der(1)(pter-q43::q43-q31.2:) (Fig. 2). Genomic DNA samples were hybridized on Affymetrix Cytogenetics Whole-Genome 2.7M arrays using the Short case report 101 0962-8827  c 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/MCD.0b013e32834e9279 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.