{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T05:41:28Z","timestamp":1761198088703,"version":"3.41.2"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T00:00:00Z","timestamp":1659571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010447","name":"Kementerian Riset, Teknologi dan Pendidikan Tinggi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Thalassemia is a monogenic, autosomal recessive, inherited disorder of the red blood cells caused by mutations or deletions in the globin gene. Approximately 6\u201310% of the Indonesian population carries the \u03b2-globin gene mutation; however, premarital screening is rarely conducted, and antenatal screening is optional. We explored the use of cell-free fetal DNA (cffDNA) as a potential non-invasive method of detecting the fetal \u03b2-globin gene mutation prenatally in pregnant women.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Pregnant mothers (<jats:italic>n<\/jats:italic> = 10), who were known carriers of thalassemia and who had a history of having borne a baby with thalassemia major, and their carrier husbands (<jats:italic>n<\/jats:italic> = 4) were recruited after providing consent. EDTA blood was drawn, and maternal DNA, including cffDNA, and paternal DNA were isolated. Maternal contamination tests were conducted using the variable number tandem repeat test for <jats:italic>ApoB<\/jats:italic> and <jats:italic>D1S80<\/jats:italic> loci. Allele quantification was performed by pyrosequencing. Known mutations from the bio-archived DNA of patients with thalassemia major (<jats:italic>n<\/jats:italic> = 16) were run alongside as a control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 7 out of 10 cffDNA successfully passed the maternal contamination test. The results of the allele quantification showed that six fetuses were predictive carriers of IVS1nt5 and one was predictive normal, in line with the allele quantification for the bio-archived DNA from patients with thalassemia major. The minimum threshold percentage for mutant A allele at cd26 was 32%, mutant T allele at IVS1nt1 was 23%, and mutant C allele at IVS1nt5 was 39%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Taking cffDNA from the mother\u2019s blood proved useful as a non-invasive means of detecting the \u03b2-globin gene mutation using pyrosequencing allele quantification. This non-invasive method is of great interest for prenatal diagnosis in settings with limited facilities, as it minimizes the risk of abortion. Further study of other mutations of the \u03b2-globin gene is needed.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2022.902879","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T05:23:25Z","timestamp":1659590605000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Cell-free fetal DNA as a non-invasive method using pyrosequencing in detecting beta-globin gene mutation: A pilot study from area with limited facilities in Indonesia"],"prefix":"10.3389","volume":"10","author":[{"given":"Ani Melani","family":"Maskoen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nurul Setia","family":"Rahayu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bremmy","family":"Laksono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azzania","family":"Fibriani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willyanti","family":"Soewondo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanes C.","family":"Mose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edhyana","family":"Sahiratmadja","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramdan","family":"Panigoro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4084\/MJHID.2017.018","article-title":"Beta-thalassemia distribution in the old world: an ancient disease seen from a historical standpoint.","volume":"9","author":"De Sanctis","year":"2017","journal-title":"Mediterr J Hematol Infect Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/gim.2016.173","article-title":"Beta-thalassemia.","volume":"19","author":"Origa","year":"2017","journal-title":"Genet Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"380","DOI":"10.3109\/03630269.2014.1003564","article-title":"Effectiveness of prenatal screening for hemoglobinopathies in a developing country.","volume":"39","author":"Choudhuri","year":"2015","journal-title":"Hemoglobin."},{"key":"B4","doi-asserted-by":"crossref","first-page":"480","DOI":"10.2471\/BLT.06.036673","article-title":"Global epidemiology of haemoglobin disorders and derived service indicators.","volume":"86","author":"Modell","year":"2008","journal-title":"Bull World Health Organ."},{"key":"B5","first-page":"578","article-title":"Feasibility and safety of chorionic villus sampling (CVS) for prenatal diagnosis of thalassemia in Bangladesh.","volume":"27","author":"Kazal","year":"2018","journal-title":"Mymensingh Med J."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.acc.2016.05.004","article-title":"Cell-free fetal DNA testing for prenatal diagnosis.","volume":"76","author":"Drury","year":"2016","journal-title":"Adv Clin Chem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"144","DOI":"10.3109\/03630269.2011.647998","article-title":"Prenatal diagnosis of hemoglobinopathies by pyrosequencing: a more sensitive and rapid approach to fetal genotyping.","volume":"36","author":"Timbs","year":"2012","journal-title":"Hemoglobin."},{"year":"2017","journal-title":"Pedoman pengendalian penyakit thalassemia di fasilitas kesehatan tingkat pertama. 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