{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:09:37Z","timestamp":1792166977286,"version":"4.4.0"},"reference-count":16,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1996,12]]},"abstract":"<jats:p>Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct developmental disorders caused by absence of paternal or maternal contributions of the chromosome region 15q11-q13, resulting from deletions, uniparental disomy (UPD), or rare imprinting mutations. Molecular cytogenetic diagnosis is currently performed using a combination of fluorescence in situ hybridisation (FISH), DNA polymorphism analysis, and DNA methylation analysis. Only methylation analysis will detect all three categories of PWS abnormalities, but its reliability in tissues other than peripheral blood has not been examined extensively. Therefore, we examined the methylation status at the CpG island of the small nuclear ribonucleoprotein associated polypeptide N (SNRPN) gene and at the PW71 locus using normal and abnormal lymphoblast (LB) cell lines (n = 48), amniotic fluid (AF) cell cultures (n = 25), cultured chorionic villus samples (CVS, n = 17), and fetal tissues (n = 18) by Southern blot analysis with methylation sensitive enzymes. Of these samples, 20 LB cell lines, three AF cultures, one CVS, and 15 fetal tissues had been previously diagnosed as having deletions or UPD by other molecular methods. Methylation status at SNRPN showed consistent results when compared with FISH or DNA polymorphism analysis using all cell types tested. However, the methylation pattern for PW71 was inconsistent when compared with other tests and should therefore not be used on tissues other than peripheral blood. We conclude that SNRPN, but not PW71, methylation analysis may be useful for diagnosis of PWS\/AS on LB cell lines, cultured amniotic fluid, or chorionic villus samples and will allow, for the first time, prenatal diagnosis for families known to carry imprinting centre defects.<\/jats:p>","DOI":"10.1136\/jmg.33.12.1011","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"1011-1014","source":"Crossref","is-referenced-by-count":43,"title":["Analysis of parent of origin specific DNA methylation at SNRPN and PW71 in tissues: implication for prenatal diagnosis."],"prefix":"10.1136","volume":"33","author":[{"given":"T","family":"Kubota","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Aradhya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Macha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A C","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L C","family":"Surh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Satish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M S","family":"Verp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H L","family":"Nee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S L","family":"Christan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D H","family":"Ledbetter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1996,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/ng0994-52","article-title":"Deletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region","volume":"8","author":"Sutcliffe, J.S.; Nakao, M.; Christian, S.","year":"1994","unstructured":"Sutcliffe JS, Nakao M, Christian S, et al. Deletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region. Nat Genet 1994;8:52-8.","journal-title":"Nat Genet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/ng0495-395","article-title":"Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome","volume":"9","author":"Buiting, K.; Saitoh, S.; Gross, S.","year":"1995","unstructured":"Buiting K, Saitoh S, Gross S, et al. Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15. Nat Genet 1995;9:395-400.","journal-title":"15. Nat Genet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1093\/hmg\/1.6.417","article-title":"et aL Molecular dissection of the Prader-Willi\/Angelman syndrome region (15qll-13) by YAC cloning and FISH analysis","volume":"1","author":"Kuwano, A.; Mutirangura, A.; Dittrich, B.","year":"1992","unstructured":"Kuwano A, Mutirangura A, Dittrich B, et aL Molecular dissection of the Prader-Willi\/Angelman syndrome region (15qll-13) by YAC cloning and FISH analysis. Hum Mol Genet 1992;1:417-25.","journal-title":"Hum Mol Genet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/(SICI)1096-8628(19960329)62:3<216::AID-AJMG3>3.0.CO;2-R","article-title":"FISH detection ofchromosome 15 deletions in Prader-Willi and Angelman syndromes","volume":"62","author":"Teshima, I.; Chadwick, D.; Chitayat, D.","year":"1996","unstructured":"Teshima I, Chadwick D, Chitayat D, et al. FISH detection ofchromosome 15 deletions in Prader-Willi and Angelman syndromes. AmJ Med Genet 1996;62:216-23.","journal-title":"AmJ Med Genet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1093\/hmg\/2.2.143","article-title":"Multiplex PCR of three dinucleotide repeats in the Prader-Willi\/ Angelman critical region","volume":"2","author":"Mutirangura, A.; Greenberg, F.; Butler, M.G.","year":"1993","unstructured":"Mutirangura A, Greenberg F, Butler MG, et al. Multiplex PCR of three dinucleotide repeats in the Prader-Willi\/ Angelman critical region (15qll-q13): molecular diagnosis and mechanism of uniparental disomy. Hum Mol Genet 1993;2:143-51.","journal-title":"Hum Mol Genet; molecular diagnosis and mechanism of uniparental disomy"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1136\/adc.72.5.397","article-title":"Comparison of high resolution cytogenetics, fluorescence in situ hybridization, and DNA studies to validate the diagnosis of Prader-Willi and Angelman's syndromes","volume":"72","author":"Smith, A.; Prasad, M.; Deng, Z.M.; Robson, L.; Woodage, T.; Trent, R.J.","year":"1995","unstructured":"Smith A, Prasad M, Deng ZM, Robson L, Woodage T, Trent RJ. Comparison of high resolution cytogenetics, fluorescence in situ hybridization, and DNA studies to validate the diagnosis of Prader-Willi and Angelman's syndromes. Arch Dis Child 1995;72:397-402.","journal-title":"Arch Dis Child"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1136\/jmg.32.2.88","article-title":"DNA methylation based testing of 450 patients suspected ofhaving Prader-Willi syndrome","volume":"32","author":"Gillessen-Kaesbach, G.; Gross, S.; Kaya-Westerloh, S.; Passarge, E.; Horsthemke, B.","year":"1995","unstructured":"Gillessen-Kaesbach G, Gross S, Kaya-Westerloh S, Passarge E, Horsthemke B. DNA methylation based testing of 450 patients suspected ofhaving Prader-Willi syndrome. JMed Genet 1995;32:88-92.","journal-title":"JMed Genet"},{"key":"ref_8","article-title":"Validation studies of SNRPN methylation as a diagnostic test for PraderWilli syndrome","author":"Kubota, T.; Sutcliffe, J.S.; Aradhya, S.","unstructured":"Kubota T, Sutcliffe JS, Aradhya S, et al. Validation studies of SNRPN methylation as a diagnostic test for PraderWilli syndrome. Am J Med Genet (in press).","journal-title":"Am J Med Genet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1007\/BF00223870","article-title":"DNA diagnosis of Prader-Willi and Angelman syndromes with the probe PW71 (D15S63)","volume":"95","author":"den Ouweland AMW, Van; der Est MN, Van; E, Wesby-van Swaay","year":"1995","unstructured":"Van den Ouweland AMW, Van der Est MN, Wesby-van Swaay E, et al. DNA diagnosis of Prader-Willi and Angelman syndromes with the probe PW71 (D15S63). Hum Genet 1995;95:562-7.","journal-title":"Hum Genet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1093\/hmg\/2.12.1995","article-title":"Characterization of a methylation imprint in the Prader-Willi syndrome chromosome region","volume":"2","author":"Dittrich, B.; Buiting, K.; Gross, S.; Horsthemke, B.","year":"1993","unstructured":"Dittrich B, Buiting K, Gross S, Horsthemke B. Characterization of a methylation imprint in the Prader-Willi syndrome chromosome region. Hum Mol Genet 1993;2: 1995-9.","journal-title":"Hum Mol Genet"},{"key":"ref_11","first-page":"1085","article-title":"American Society of Human Genetics\/American College of Medical Genetics Test and Technology Transfer Committee. Diagnostic testing for Prader-Willi and Angelman syndromes: report of the ASHG\/ACMG test and technology transfer committee","volume":"58","year":"1996","unstructured":"American Society of Human Genetics\/American College of Medical Genetics Test and Technology Transfer Committee. Diagnostic testing for Prader-Willi and Angelman syndromes: report of the ASHG\/ACMG test and technology transfer committee. Am J7 Hum Genet 1996;58: 1085-8.","journal-title":"Am J7 Hum Genet"},{"key":"ref_12","first-page":"572","article-title":"Deletion and uniparental disomy involving the same maternal chromosome","volume":"330","author":"Surh, L.S.; Wang, H.; Hunter, A.G.W.","year":"1994","unstructured":"Surh LS, Wang H, Hunter AGW. Deletion and uniparental disomy involving the same maternal chromosome 15. N Engl 7 Med 1994;330:572-3."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/(SICI)1097-0223(199604)16:4<323::AID-PD856>3.0.CO;2-5","article-title":"Prenatal diagnosis of uniparental disomy 15 following trisomy 15 mosaicism","volume":"16","author":"Christian, S.L.; Smith, A.C.M.; Macha, M.","year":"1996","unstructured":"Christian SL, Smith ACM, Macha M, et al. Prenatal diagnosis of uniparental disomy 15 following trisomy 15 mosaicism. Prenat Diagn 1996;16:323-32.","journal-title":"Prenat Diagn"},{"key":"ref_14","first-page":"313","article-title":"Molecular diagnosis of the Prader-Willi and Angelman syndromes by detection of parent-of-origin specific DNA methylation in 15qll-13","volume":"90","author":"Dittrich, B.; Robinson, W.P.; Knoblauch, H.","year":"1992","unstructured":"Dittrich B, Robinson WP, Knoblauch H, et al. Molecular diagnosis of the Prader-Willi and Angelman syndromes by detection of parent-of-origin specific DNA methylation in 15qll-13. Hum Genet 1992;90:313-15.","journal-title":"Hum Genet"},{"key":"ref_15","first-page":"1377","article-title":"Modification of 15q 11 -q 13 DNA methylation imprints in unique Angelman and Prader-Willi patients","volume":"3","author":"Glenn, C.C.; Nicholls, R.D.; Robinson, W.P.","year":"1993","unstructured":"Glenn CC, Nicholls RD, Robinson WP, et al. Modification of 15q 11 -q 13 DNA methylation imprints in unique Angelman and Prader-Willi patients. Hum Mol Genet 1993;3: 1377-82.","journal-title":"Hum Mol Genet"},{"key":"ref_16","first-page":"335","article-title":"Gene structure, DNA methylation, and imprinted expression ofthe human SNRPN gene","volume":"58","author":"Glenn, C.C.; Saitoh, S.; Jong, M.T.C.","year":"1996","unstructured":"Glenn CC, Saitoh S, Jong MTC, et al. Gene structure, DNA methylation, and imprinted expression ofthe human SNRPN gene. Am _7 Hum Genet 1996;58:335-46.","journal-title":"Am _7 Hum Genet"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.33.12.1011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T19:36:12Z","timestamp":1760729772000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.33.12.1011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,12]]},"references-count":16,"journal-issue":{"issue":"12","published-online":{"date-parts":[[1996,12,1]]},"published-print":{"date-parts":[[1996,12]]}},"alternative-id":["10.1136\/jmg.33.12.1011"],"URL":"https:\/\/doi.org\/10.1136\/jmg.33.12.1011","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,12]]}}}