{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T13:54:25Z","timestamp":1783605265908,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T00:00:00Z","timestamp":1716422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Celocentesis is a new sampling tool for prenatal diagnosis available from 7 weeks in case of couples at risk for genetic diseases. In this study, we reported the feasibility of earlier prenatal diagnosis by celocentesis in four cases of cystic fibrosis and one case of cystic fibrosis and \u03b2-thalassemia co-inherited in the same fetus. Celomic fluids were aspired from the celomic cavity between 8+2 and 9+3 weeks of gestation and fetal cells were picked up by micromanipulator. Maternal DNA contamination was tested and target regions of fetal DNA containing parental pathogenetic variants of CFTR and HBB genes were amplified and sequenced. Four of the five fetuses resulted as being affected by cystic fibrosis and, in all cases, the women decided to interrupt the pregnancy. In the other case, the fetus presented a healthy carrier of cystic fibrosis. The results were confirmed in three cases on placental tissue. In one case, no abortive tissue was obtained. In the last case, the woman refused the prenatal diagnosis to confirm the celocentesis data; the pregnancy is ongoing without complications. This procedure provides prenatal diagnosis of monogenic diseases at least four weeks earlier than traditional procedures, reducing the anxiety of patients and providing the option for medical termination of the affected fetus at 8\u201310 weeks of gestation, which is less traumatic and safer than surgical termination in the second trimester.<\/jats:p>","DOI":"10.3390\/genes15060662","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T05:35:20Z","timestamp":1716442520000},"page":"662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Prenatal Diagnosis of Cystic Fibrosis by Celocentesis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5147-9547","authenticated-orcid":false,"given":"Antonino","family":"Giambona","sequence":"first","affiliation":[{"name":"Unit of Molecular Diagnosis of Rare Hematological Diseases, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Vinciguerra","sequence":"additional","affiliation":[{"name":"Unit of Molecular Diagnosis of Rare Hematological Diseases, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Leto","sequence":"additional","affiliation":[{"name":"Unit of Molecular Diagnosis of Rare Hematological Diseases, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Cassar\u00e0","sequence":"additional","affiliation":[{"name":"Unit of Molecular Diagnosis of Rare Hematological Diseases, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Marchese","sequence":"additional","affiliation":[{"name":"Unit of Molecular Diagnosis of Rare Hematological Diseases, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8127-8263","authenticated-orcid":false,"given":"Valentina","family":"Cigna","sequence":"additional","affiliation":[{"name":"Unit of Fetal Medicine and Prenatal Diagnosis, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Orlandi","sequence":"additional","affiliation":[{"name":"Unit of Fetal Medicine and Prenatal Diagnosis, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elena","family":"Mugavero","sequence":"additional","affiliation":[{"name":"Unit of Fetal Medicine and Prenatal Diagnosis, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaspare","family":"Cucinella","sequence":"additional","affiliation":[{"name":"Unit of Fetal Medicine and Prenatal Diagnosis, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelio","family":"Maggio","sequence":"additional","affiliation":[{"name":"Unit of Hematology for Rare Hematological Diseases, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Termini","sequence":"additional","affiliation":[{"name":"Ospedale dei Bambini G. Di Cristina, ARNAS Civico, 90134 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Makrydimas","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"D\u2019Alcamo","sequence":"additional","affiliation":[{"name":"Unit of Molecular Diagnosis of Rare Hematological Diseases, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Picciotto","sequence":"additional","affiliation":[{"name":"Unit of Fetal Medicine and Prenatal Diagnosis, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,23]]},"reference":[{"key":"ref_1","unstructured":"(2024, March 05). Available online: http:\/\/www.orphadata.org\/cgi-bin\/epidemio.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1016\/S0140-6736(09)60327-5","article-title":"Cystic fibrosis","volume":"373","author":"Sullivan","year":"2009","journal-title":"Lancet"},{"key":"ref_3","first-page":"704","article-title":"Inherited haemoglobin disorders: An increasing global health problem","volume":"79","author":"Weatherall","year":"2001","journal-title":"Bull. World Health Organ."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jcf.2006.05.008","article-title":"A survey of newborn screening for cystic fibrosis in Europe","volume":"6","author":"Southern","year":"2007","journal-title":"J. Cyst. Fibros."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/(SICI)1097-0258(19960315)15:5<449::AID-SIM173>3.0.CO;2-X","article-title":"The incidence of cystic fibrosis","volume":"15","author":"Kosorok","year":"1996","journal-title":"Stat. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1126\/science.2772657","article-title":"Identification of the cystic fibrosis gene: Chromosome walking and jumping","volume":"245","author":"Rommens","year":"1989","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1126\/science.2475911","article-title":"Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA","volume":"245","author":"Riordan","year":"1989","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1126\/science.2570460","article-title":"Identification of the cystic fibrosis gene: Genetic analysis","volume":"245","author":"Kerem","year":"1989","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1002\/ppul.1950110704","article-title":"Current issues in neonatal screening for cystic fibrosis and implications of the CF gene discovery","volume":"7","author":"Farrell","year":"1991","journal-title":"Pediatr. Pulmonol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/S0140-6736(00)02652-0","article-title":"Neonatal Screening for Cystic Fibrosis in Brittany, France: Assessment of 10 Years\u2019 Experience and Impact on Prenatal Diagnosis","volume":"356","author":"Scotet","year":"2000","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1749-6632.1998.tb10482.x","article-title":"Global epidemiology of hemoglobin disorders","volume":"850","author":"Angastiniotis","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1080\/00365510601046557","article-title":"Epidemiology of Haemoglobin Disorders in Europe: An overview","volume":"67","author":"Modell","year":"2007","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1046\/j.1525-1381.1999.99235.x","article-title":"Thalassemia and malaria: New insights into and an old problem","volume":"111","author":"Clegg","year":"1999","journal-title":"Proc. Assoc. Am. Phys."},{"key":"ref_14","first-page":"76","article-title":"Current status of thalassaemia and the sickle cell syndromes in Greece","volume":"33","author":"Loukopoulos","year":"1996","journal-title":"Semin. Hematol."},{"key":"ref_15","first-page":"592","article-title":"Prevention of homozygous b thalassaemia by carrier screening and prenatal diagnosis in Sardinia","volume":"33","author":"Cao","year":"1981","journal-title":"Am. J. Hum. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0950-3536(98)80071-1","article-title":"\u03b2-thalassaemia","volume":"11","author":"Thein","year":"1998","journal-title":"Baillieres Clin. Haematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1007\/s00431-023-04900-w","article-title":"Therapeutic perspective for children and young adults living with thalassemia and sickle cell disease","volume":"182","author":"Ferraresi","year":"2023","journal-title":"Eur. J. Pediatr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s00439-009-0669-y","article-title":"Population programs for the detection of couples at risk for severe monogenic genetic diseases","volume":"126","author":"Zlotogora","year":"2009","journal-title":"Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-4939-8889-1_1","article-title":"Traditional Prenatal Diagnosis: Past to Present","volume":"1885","author":"Levy","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.ejogrb.2020.08.001","article-title":"Non-invasive prenatal diagnosis and screening for monogenic disorders","volume":"253","author":"Scotchman","year":"2020","journal-title":"Eur. J. Obs. Gynecol. Reprod. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.tjog.2015.05.002","article-title":"Noninvasive prenatal diagnosis","volume":"54","author":"Cheng","year":"2015","journal-title":"Taiwan. J. Obs. Gynecol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1056\/NEJM199812103392402","article-title":"Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma","volume":"339","author":"Lo","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/pd.4124","article-title":"The clinical implementation of non-invasive prenatal diagnosis for single-gene disorders: Challenges and progress made","volume":"33","author":"Lench","year":"2013","journal-title":"Prenat. Diagn."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1111\/1471-0528.15045","article-title":"Non-invasive prenatal testing for fetal inheritance of maternal \u03b2-thalassaemia mutations using targeted sequencing and relative mutation dosage: A feasibility study","volume":"125","author":"Xiong","year":"2018","journal-title":"BJOG"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1002\/uog.12331","article-title":"Fetal fraction in maternal plasma cell-free DNA at 11\u201313 weeks\u2019 gestation: Relation to maternal and fetal characteristics","volume":"41","author":"Ashoor","year":"2013","journal-title":"Ultrasound Obs. Gynecol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Pacault, M., Verebi, C., Champion, M., Orhant, L., Perrier, A., Girodon, E., Leturcq, F., Vidaud, D., F\u00e9rec, C., and Bienvenu, T. (2023). Non-invasive prenatal diagnosis of single gene disorders with enhanced relative haplotype dosage analysis for diagnostic implementation. PLoS ONE, 24.","DOI":"10.1101\/2023.01.13.23284512"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Carbone, L., Cariati, F., Sarno, L., Conforti, A., Bagnulo, F., Strina, I., Pastore, L., Maruotti, G.M., and Alviggi, C. (2020). Non-Invasive Prenatal Testing: Current Perspectives and Future Challenges. Genes, 12.","DOI":"10.3390\/genes12010015"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cca.2014.12.026","article-title":"New trend in non-invasive prenatal diagnosis","volume":"451","author":"Ferrari","year":"2015","journal-title":"Clin. Chim. Acta"},{"key":"ref_29","first-page":"28","article-title":"Prenatal genetic diagnosis of monogenic diseases. Prenatal Diagnosis Commission and the Genetics Commission of the Spanish Society of Laboratory Medicine","volume":"24","author":"Macher","year":"2023","journal-title":"Adv. Lab. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1016\/S0140-6736(94)90182-1","article-title":"Analysis of limb reduction defects in babies exposed to chorionic villus sampling","volume":"343","author":"Firth","year":"1994","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Canadian Early and Mid trimester Amniocentesis Trial (CEMAT) Group (1998). Randomised trial to assess safety and fetal outcome of early and midtrimester amniocentesis. Lancet, 351, 242\u2013247.","DOI":"10.1016\/S0140-6736(97)12346-7"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1016\/0140-6736(93)90761-5","article-title":"Coelocentesis: A new technique for early prenatal diagnosis","volume":"341","author":"Jurkovic","year":"1993","journal-title":"Lancet"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1365-2141.2011.08621.x","article-title":"Feasibility of DNA diagnosis of haemoglobinopathies on coelocentesis","volume":"153","author":"Giambona","year":"2011","journal-title":"Br. J. Haematol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1093\/oxfordjournals.humrep.a019158","article-title":"Rapid genetic diagnosis at 7\u20139 weeks gestation: Diagnosis of sex, single gene defects and DNA fingerprint from coelomic samples","volume":"11","author":"Findlay","year":"1996","journal-title":"Hum. Reprod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1002\/(SICI)1097-0223(199706)17:6<588::AID-PD116>3.0.CO;2-U","article-title":"Turner\u2019s syndrome 45, X found by celocentesis","volume":"17","author":"Cruger","year":"1997","journal-title":"Prenat. Diagn."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1093\/humrep\/del143","article-title":"Very early prenatal diagnosis of genetic diseases based on coelomic fluid analysis: A feasibility study","volume":"21","author":"Jouannic","year":"2006","journal-title":"Hum. Reprod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4129","DOI":"10.1242\/dev.126.18.4129","article-title":"Coelom formation: Binary decision of the lateral plate mesoderm is controlled by the ectoderm","volume":"126","author":"Funayama","year":"1999","journal-title":"Development"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1159\/000070807","article-title":"Evolution of the amniotic sac and extracelomic space as seen by early ultrasound examination","volume":"18","author":"Morgan","year":"2003","journal-title":"Fetal Diagn. Ther."},{"key":"ref_39","first-page":"311","article-title":"Catalog of solutes measured in paired extraembryonic celomic fluid and maternal serum samples","volume":"518","year":"2006","journal-title":"J. Reprod. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10973","DOI":"10.1038\/s41598-018-29384-9","article-title":"Human coelomic fluid investigation: A MS-based analytical approach to prenatal screening","volume":"8","author":"Aiello","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/pd.4793","article-title":"Embryo-fetal erythroid cell selection from celomic fluid allows earlier prenatal diagnosis of hemoglobinopathies","volume":"36","author":"Giambona","year":"2016","journal-title":"Prenat. Diagn."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1002\/pd.4922","article-title":"Identification of embryo fetal cells in celomic fluid using morphological and short-tandem repeats analysis","volume":"36","author":"Giambona","year":"2016","journal-title":"Prenat. Diagn."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1111\/aogs.13287","article-title":"Fetal aneuploidy diagnosed at celocentesis for early prenatal diagnosis of congenital hemoglobinopathies","volume":"97","author":"Giambona","year":"2018","journal-title":"Acta Obs. Gynecol. Scand."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1002\/uog.22059","article-title":"Celocentesis for early prenatal diagnosis of hemoglobinopathy","volume":"56","author":"Makrydimas","year":"2020","journal-title":"Ultrasound Obs. Gynecol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/jcla.20083","article-title":"Modified salting-out method: High-yield, high-quality genomic DNA extraction from whole blood using laundry detergent","volume":"19","author":"Nasiri","year":"2005","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1093\/molehr\/gah108","article-title":"Rapid prenatal diagnosis of common chromosome aneuploidies by QF-PCR: Assessment on 18,000 consecutive clinical samples","volume":"10","author":"Cirigliano","year":"2004","journal-title":"Mol. Hum. Reprod."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s40291-022-00577-3","article-title":"Celomic Fluid: Laboratory Workflow for Prenatal Diagnosis of Monogenic Diseases","volume":"26","author":"Giambona","year":"2022","journal-title":"Mol. Diagn. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1080\/01443615.2021.2014429","article-title":"Very early prenatal diagnosis of Cockayne\u2019s syndrome by coelocentesis","volume":"42","author":"Giambona","year":"2022","journal-title":"J. Obs. Gynaecol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1111\/ijlh.13837","article-title":"Early prenatal diagnosis of Hb Lepore Boston-Washington and \u03b2-thalassemia on fetal celomatic DNA","volume":"44","author":"Giambona","year":"2022","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1080\/03630269.2023.2167659","article-title":"Celocentesis for Early Prenatal Diagnosis in Couples at-Risk for \u03b2-Thalassemia and Sicilian (\u03b4\u03b2)0-Thalassemia","volume":"46","author":"Giambona","year":"2022","journal-title":"Hemoglobin"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/6\/662\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:46:56Z","timestamp":1760107616000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/6\/662"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,23]]},"references-count":50,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["genes15060662"],"URL":"https:\/\/doi.org\/10.3390\/genes15060662","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,23]]}}}