{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T17:12:01Z","timestamp":1771002721746,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,12,14]],"date-time":"2005-12-14T00:00:00Z","timestamp":1134518400000},"content-version":"vor","delay-in-days":3910,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[1995,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We report the results of carrier and prenatal diagnosis for hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency, Lesch\u2014Nyhan syndrome, by carrier testing of 83 women and prenatal analysis of 26 pregnancies. Our diagnostic methodologies include mutation detection and linkage analysis for probands and their families and biochemical measurement of HPRT enzyme activity for at\u2010risk pregnancies. Identification of the mutation in the index case of each family permits precise carrier diagnosis using polymerase chain reaction (PCR) amplification of HPRT gene sequences and automated DNA sequencing. We demonstrate 100 per cent sensitivity for the detection of mutations in the HPRT gene of affected males and highly efficient carrier testing of at\u2010risk females. Two other molecular methods proven to have high utility include PCR\u2010based dosage analysis and linkage analysis by PCR amplification of a short tandem repeat (STR) in intron 3 of the HPRT gene. As a result, 45 at\u2010risk women, 56 per cent of those tested, were identified not to be carriers of their family's HPRT gene mutation. Seven of these women were the mothers of affected males and prenatal testing for future pregnancies was recommended because of the possibility of gonadal mosaicism. Thirty\u2010eight of these women were more distant relatives of affected males, thereby eliminating the need for future prenatal procedures. These studies illustrate the utility and precision of molecular methodologies for carrier and prenatal diagnosis of Lesch\u2014Nyhan syndrome. These studies also illustrate that molecular diagnostic studies of affected males and carrier testing prior to pregnancy can clarify genetic risk predictions and eliminate unnecessary prenatal procedures.<\/jats:p>","DOI":"10.1002\/pd.1970150406","type":"journal-article","created":{"date-parts":[[2007,3,4]],"date-time":"2007-03-04T11:05:35Z","timestamp":1173006335000},"page":"329-338","source":"Crossref","is-referenced-by-count":18,"title":["Lesch\u2014Nyhan syndrome: Carrier and prenatal diagnosis"],"prefix":"10.1002","volume":"15","author":[{"given":"R. L.","family":"Alford","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. B.","family":"Redman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. E.","family":"O'brien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. T.","family":"Caskey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,12,14]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"190","article-title":"Rapid and efficient resolution of parentage by amplification of short tandem repeats","volume":"55","author":"Afford R. L.","year":"1994","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_2_1_3_1","first-page":"951","article-title":"Carrier detection and prenatal diagnosis in Duchenne and Becker muscular dystrophy families, using dinucleotide repeat polymorphisms","volume":"49","author":"Clemens P. R.","year":"1991","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00200907"},{"key":"e_1_2_1_5_1","first-page":"620","article-title":"Intragenic deletions in 21 Duchenne muscular dystrophy (DMD)\/Becker muscular dystrophy (BMD) families studied with the dystrophin cDNA: location of breakpoints on Hind III and Bgl II exon\u2013containing fragment maps, meiotic and mitotic origin of the mutations","volume":"43","author":"Darras B. T.","year":"1988","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(90)90493-E"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(73)80123-4"},{"key":"e_1_2_1_8_1","first-page":"123","article-title":"The occurrence of new mutations in the X\u2010linked recessive Lesch\u2014Nyhan disease","volume":"28","author":"Francke U.","year":"1976","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_2_1_9_1","unstructured":"Francke U. Winter R. M. Lin D. Bakay B. Seegmiller J. E. Nyhan W. L.(1981). Use of carrier detection tests to estimate male to female ratio of mutation rates in Lesch\u2014Nyhan disease. In: Hook E. B. Porter I. H. (Eds).Population and Biological Aspects of Human Mutation New York:117\u2013130."},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.172.3983.572"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.6.1919"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(90)90545-6"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.68.7.1425"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.1970090620"},{"key":"e_1_2_1_15_1","first-page":"252","volume-title":"Regulation of Purine Biosynthesis, American Chemical Society Monograph","author":"Henderson J. 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