{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T00:33:14Z","timestamp":1760747594604,"version":"build-2065373602"},"reference-count":27,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1989,6]]},"abstract":"<jats:p>In the Mediterranean area, 50% of the beta thalassaemia mutations abolish or create a restriction endonuclease site in the beta globin gene. This study describes a new procedure for prenatal detection of these beta thalassaemia defects based on the direct visualisation, on an ethidium bromide stained polyacrylamide gel, of the discrete DNA fragments produced by restriction endonuclease digestion of fetal DNA, enzymatically amplified using the DNA polymerase from the thermophilus bacterium Thermus aquaticus. We applied this procedure to the Sardinian population to detect the nonsense mutation at codon 39 and the frameshift at codon 6 of the beta globin gene; these are the most frequent beta thalassaemia mutations in this population, accounting for 95% and 2.2% of the beta thalassaemia chromosomes. The main advantages of this procedure are simplicity (no radioactivity), sensitivity (0.2 microgram of DNA), and rapidity (12 hours). The very small amount of fetal material required makes amniotic fluid cell culture unnecessary and may decrease the fetal loss rate associated with trophoblast sampling. By circumventing the use of radioactive and non-radioactive probes, the spread of this technology to the high risk areas will be facilitated.<\/jats:p>","DOI":"10.1136\/jmg.26.6.363","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:11:11Z","timestamp":1226329871000},"page":"363-367","source":"Crossref","is-referenced-by-count":19,"title":["Prenatal diagnosis of beta thalassaemia based on restriction endonuclease analysis of amplified fetal DNA."],"prefix":"10.1136","volume":"26","author":[{"given":"M","family":"Pirastu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M S","family":"Ristaldi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1989,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/j.1365-2141.1986.tb05543.x","article-title":"The prenatal diagnosis of 13 thalassaemia","volume":"63","author":"Cao, A.; Pirastu, M.; Rosatelli, C.","year":"1986","unstructured":"Cao A, Pirastu M, Rosatelli C. The prenatal diagnosis of 13 thalassaemia. Br J Haematol 1986;63:215-20.","journal-title":"Br J Haematol"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7789","DOI":"10.1093\/nar\/11.22.7789","article-title":"A 13 thalassaemia lesion abolishes the same MstII site as the sickle mutation","volume":"11","author":"Chang, J.C.; Alberti, A.; Kan, Y.W.","year":"1983","unstructured":"Chang JC, Alberti A, Kan YW. A 13 thalassaemia lesion abolishes the same MstII site as the sickle mutation. Nucleic Acids Res 1983;11:7789-94.","journal-title":"Nucleic Acids Res"},{"key":"ref_3","first-page":"1095","article-title":"Direct detection of 13039 thalassaemia mutation with MaeI digestion","volume":"i:","author":"Weatherall, D.J.; Sampietro, M.; Fiorelli, G.","year":"1985","unstructured":"Weatherall DJ, Sampietro M, Fiorelli G. Direct detection of 13039 thalassaemia mutation with MaeI digestion. Lancet 1985;i: 1095.","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1172\/JCI110826","article-title":"Direct detection of the common Mediterranean 13 thalassaemia gene with synthetic DNA probes. An alternative approach for prenatal diagnosis","volume":"71","author":"Orkin, S.H.; Markham, A.F.; Kazazian, H.H.","year":"1983","unstructured":"Orkin SH, Markham AF, Kazazian HH. Direct detection of the common Mediterranean 13 thalassaemia gene with synthetic DNA probes. An alternative approach for prenatal diagnosis. J Clin Invest 1983;71:775-9.","journal-title":"J Clin Invest"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1056\/NEJM198308043090506","article-title":"Prenatal diagnosis of 1-thalassemia. Detection of a single nucleotide mutation in DNA","volume":"309","author":"Pirastu, M.; Kan, Y.W.; Cao, A.; Conner, B.J.; Teplitz, R.L.; Wallace, R.B.","year":"1983","unstructured":"Pirastu M, Kan YW, Cao A, Conner BJ, Teplitz RL, Wallace RB. Prenatal diagnosis of 1-thalassemia. Detection of a single nucleotide mutation in DNA. N Engl J Med 1983;309:284-7.","journal-title":"N Engl J Med"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0140-6736(85)91026-8","article-title":"Prenatal diagnosis of 13 thalassaemia with the synthetic oligomer technique","volume":"ii:","author":"Rosatelli, C.; Falchi, A.M.; Scalas, M.T.","year":"1985","unstructured":"Rosatelli C, Falchi AM, Scalas MT, et al. Prenatal diagnosis of 13 thalassaemia with the synthetic oligomer technique. Lancet 1985;ii:241-3.","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0140-6736(85)92493-6","article-title":"Feasibility of prenatal diagnosis of 13 thalassaemia with synthetic DNA probes in two Mediterranean populations","volume":"ii:","author":"Thein, S.L.; Waincoat, J.S.; Old, J.M.","year":"1985","unstructured":"Thein SL, Waincoat JS, Old JM. Feasibility of prenatal diagnosis of 13 thalassaemia with synthetic DNA probes in two Mediterranean populations. Lancet 1985;ii:345-7.","journal-title":"Lancet"},{"key":"ref_8","first-page":"274","article-title":"Prenatal diagnosis of the most common Mediterranean 13 thalassaemia mutants by the oligonucleotide technique","volume":"i:","author":"Loi, A.; Pirastu, M.; Cao, A.; Ulbridh, R.; Hansman, I.","year":"1986","unstructured":"Loi A, Pirastu M, Cao A, Ulbridh R, Hansman I. Prenatal diagnosis of the most common Mediterranean 13 thalassaemia mutants by the oligonucleotide technique. Lancet 1986;i:274.","journal-title":"Lancet"},{"key":"ref_9","first-page":"1125","article-title":"Direct gene analysis of chorionic villi: a possible technique for first trimester antenatal diagnosis of haemoglobinopathies","volume":"ii:","author":"Williamson, R.; Eskdale, J.; Coleman, D.V.; Niazi, M.; Loeffler, F.E.; Modell, B.","year":"1981","unstructured":"Williamson R, Eskdale J, Coleman DV, Niazi M, Loeffler FE, Modell B. Direct gene analysis of chorionic villi: a possible technique for first trimester antenatal diagnosis of haemoglobinopathies..Lancet 1981;ii:1125-7.","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/S0140-6736(85)91272-3","article-title":"Chorionic villus sampling: evaluating safety and efficacy","volume":"i:","author":"Modell, B.","year":"1985","unstructured":"Modell B. Chorionic villus sampling: evaluating safety and efficacy. Lancet 1985;i:737-40.","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/324163a0","article-title":"Analysis of enzymatically amplified 13 globin and HLA-DQ DNA with allele specific oligonucleotide probes","volume":"324","author":"Saiki, R.K.; Bugawan, T.L.; Horn, T.; Muilis, K.B.; Erlich, H.A.","year":"1986","unstructured":"Saiki RK, Bugawan TL, Horn T, Muilis KB, Erlich HA. Analysis of enzymatically amplified 13 globin and HLA-DQ DNA with allele specific oligonucleotide probes. Nature 1986; 324:163-6.","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/329293b0","article-title":"Detection of sickle cell anaemia and thalassaemia","volume":"329","author":"Chehab, F.F.; Doherty, M.; Cai, S.; Kan, Y.W.; Cooper, S.; Rubin, E.M.","year":"1987","unstructured":"Chehab FF, Doherty M, Cai S, Kan YW, Cooper S, Rubin EM. Detection of sickle cell anaemia and thalassaemia. Nature 1987;329:293-4.","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1172\/JCI110323","article-title":"thalassaemia in Sardinia is caused by a nonsense mutation","volume":"68","author":"Trecartin, R.F.; Liebhaber, S.A.; Chang, J.C.","year":"1981","unstructured":"Trecartin RF, Liebhaber SA, Chang JC, et al. 13 thalassaemia in Sardinia is caused by a nonsense mutation. J Clin Invest 1981;68: 1012-7.","journal-title":"J Clin Invest"},{"key":"ref_14","first-page":"1028","article-title":"thalassemia due to deletion of the nucleotide which is substituted in sickle cell anemia","volume":"35","author":"HH, Jr, Kazazian; SH, Orkin; CD, Boehm; JP, Sexton; SE, Antonarakis","year":"1983","unstructured":"Kazazian HH Jr, Orkin SH, Boehm CD, Sexton JP, Antonarakis SE. 13 thalassemia due to deletion of the nucleotide which is substituted in sickle cell anemia. Am J Hum Genet 1983;35: 1028-33.","journal-title":"Am J Hum Genet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1136\/jmg.24.2.97","article-title":"thalassaemia mutations in Sardinians: implications for prenatal diagnosis","volume":"24","year":"1987","unstructured":"Rosatelli C, Leoi iGB, Tuveri T, Scalas MT, Di Tucci -A, Cao A. 13 thalassaemia mutations in Sardinians: implications for prenatal diagnosis. J Med Genet 1987;24:97-100.","journal-title":"J Med Genet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1056\/NEJM198310063091405","article-title":"Prenatal diagnosis of sickle cell anemia in the first trimester of pregnancy","volume":"309","author":"Goossens, M.; Dumez, Y.; Kaplan, L.","year":"1983","unstructured":"Goossens M, Dumez Y, Kaplan L, et al. Prenatal diagnosis of sickle cell anemia in the first trimester of pregnancy. N Engl J Med 1983;309:831-3.","journal-title":"N Engl J Med"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1126\/science.2999980","article-title":"Enzymatic amplification of 13 globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia","volume":"230","author":"Saiki, R.K.; Scharf, S.; Faloona, F.","year":"1985","unstructured":"Saiki RK, Scharf S, Faloona F, et al. Enzymatic amplification of 13 globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 1985;230:1350-4.","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0076-6879(87)55023-6","article-title":"Specific synthesis of DNA in vitro via a polymerase-catalized chain reaction","volume":"155","author":"Mullis, K.B.; Faloona, F.A.","year":"1987","unstructured":"Mullis KB, Faloona FA. Specific synthesis of DNA in vitro via a polymerase-catalized chain reaction. Methods Enzymol 1987; 155:335-52.","journal-title":"Methods Enzymol"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1128\/JB.127.3.1550-1557.1976","article-title":"Deoxyribonucleic acid polymerase from the extreme thermophilus thermus acquaticus","volume":"127","author":"Chien, A.; Edgar, D.B.; Trela, J.M.","year":"1976","unstructured":"Chien A, Edgar DB, Trela JM. Deoxyribonucleic acid polymerase from the extreme thermophilus thermus acquaticus. J Bacteriol 1976;127:1550-7.","journal-title":"J Bacteriol"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1056\/NEJM198710153171603","article-title":"An improved method for prenatal diagnosis of genetic disease by analysis of amplified DNA sequences","volume":"317","author":"Kogan, C.S.; Doherty, M.; Gitschier, J.","year":"1987","unstructured":"Kogan CS, Doherty M, Gitschier J. An improved method for prenatal diagnosis of genetic disease by analysis of amplified DNA sequences. N Engl J Med 1987;317:985-90.","journal-title":"N Engl J Med"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1007\/BF00278196","article-title":"The peculiar spectrum of 1-thalassaemia genes in Tunisia","volume":"78","author":"Chibani, J.; Vidaud, M.; Duquesnoy, P.","year":"1988","unstructured":"Chibani J, Vidaud M, Duquesnoy P, et al. The peculiar spectrum of 1-thalassaemia genes in Tunisia. Hum Genet 1988;78:190-2.","journal-title":"Hum Genet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/BF00291226","article-title":"thalassaemia mutations in the Portuguese population","volume":"78","author":"Coutinho-Gomes, M.P.; Gomes da Costa, M.G.; Braga, L.B.","year":"1988","unstructured":"Coutinho-Gomes MP, Gomes da Costa MG, Braga LB, et al. 13 thalassaemia mutations in the Portuguese population. Hum Genet 1988;78:13-15.","journal-title":"Hum Genet"},{"key":"ref_23","first-page":"4218","article-title":"A nucleotide change at a splice junction in the human 13 globin gene is associated","volume-title":"with 130 thalassemia. Proc Natl Acad Sci","volume":"78","author":"Baird, M.; Driscoll, C.; Scheriner, H.","year":"1981","unstructured":"Baird M, Driscoll C, Scheriner H, et al. A nucleotide change at a splice junction in the human 13 globin gene is associated with 130 thalassemia. Proc Natl Acad Sci USA 1981;78:4218-21."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/296627a0","article-title":"Linkage of 13 thalassaemia mutations and 13 globin gene polymorphisms with DNA polymorphisms in human 13 globin gene cluster","volume":"296","author":"Orkin, S.H.; Kazazian, H.H.; Antonarakis, S.E.","year":"1982","unstructured":"Orkin SH, Kazazian HH, Antonarakis SE, et al. Linkage of 13 thalassaemia mutations and 13 globin gene polymorphisms with DNA polymorphisms in human 13 globin gene cluster. Nature 1982;296:627-31.","journal-title":"Nature"},{"key":"ref_25","first-page":"247","article-title":"127 Ala-Ser presenting as a silent 13 thalassemia","volume":"147","author":"Arous, N.; Galacteros, F.; Fessas, P.","year":"1983","unstructured":"Arous N, Galacteros F, Fessas P, et al. Hemoglobin Knossos, 127 Ala-Ser presenting as a silent 13 thalassemia. FEBS Lea 1983;147:247-50.","journal-title":"FEBS Lea"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"529","DOI":"10.3109\/03630268408991739","article-title":"Characterization of the 13 thalassemia mutation in a homozy27 gous Yugoslavian patient","volume":"8","author":"Gilman, J.G.; Huismann, T.H.J.; Stojanouski, N.; Efremov, G.D.","year":"1984","unstructured":"Gilman JG, Huismann THJ, Stojanouski N, Efremov GD. Characterization of the 13 thalassemia mutation in a homozy27 gous Yugoslavian patient. Hemoglobin 1984;8:529-33.","journal-title":"Hemoglobin"},{"key":"ref_27","first-page":"15969","article-title":"Molecular analysis of deletion and deletion hereditary persistence of fetal hemoglobin and identification of a new mutation causing f1-thalassemia","volume":"445","author":"Feingold, E.A.; Collins, F.S.; Metherall, J.E.; CJ, Jr, Stockert; Weissman, S.M.; Forget, B.G.","year":"1985","unstructured":"Feingold EA, Collins FS, Metherall JE, Stockert CJ Jr, Weissman SM, Forget BG. Molecular analysis of deletion and deletion hereditary persistence of fetal hemoglobin and identification of a new mutation causing f1-thalassemia. Ann NY Acad Sci 1985;445:15969.","journal-title":"Acad Sci"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.26.6.363","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T18:14:09Z","timestamp":1760724849000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.26.6.363"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1989,6]]},"references-count":27,"journal-issue":{"issue":"6","published-online":{"date-parts":[[1989,6,1]]},"published-print":{"date-parts":[[1989,6]]}},"alternative-id":["10.1136\/jmg.26.6.363"],"URL":"https:\/\/doi.org\/10.1136\/jmg.26.6.363","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"type":"print","value":"0022-2593"},{"type":"electronic","value":"1468-6244"}],"subject":[],"published":{"date-parts":[[1989,6]]}}}