{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T16:18:13Z","timestamp":1769098693475,"version":"3.49.0"},"reference-count":49,"publisher":"BMJ","issue":"1","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2000,10,9]]},"published-print":{"date-parts":[[2001,1,1]]},"abstract":"<jats:sec>\n                  <jats:title>CONTEXT<\/jats:title>\n                  <jats:p>Chromosomal abnormalities that involve the proximal region of chromosome 15q occur relatively frequently in the human population. However, interstitial triplications involving one 15 homologue are very rare with three cases reported to date.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>To provide a detailed molecular characterisation of four additional patients with interstitial triplications of chromosome 15q11-q14.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>DESIGN<\/jats:title>\n                  <jats:p>Molecular analyses were performed using DNA markers and probes specific for the 15q11-q14 region.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SETTING<\/jats:title>\n                  <jats:p>Molecular cytogenetics laboratory at the University of Chicago.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SUBJECTS<\/jats:title>\n                  <jats:p>Four patients with mild to severe mental retardation and features of Prader-Willi syndrome (PWS) or Angelman syndrome (AS) were referred for molecular cytogenetic analysis following identification of a suspected duplication\/triplication of chromosome 15q11-q14 by routine cytogenetic analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>MAIN OUTCOME MEASURES<\/jats:title>\n                  <jats:p>Fluorescence in situ hybridisation (FISH) was performed to determine the type of chromosomal abnormality present, the extent of the abnormal region, and the orientation of the extra chromosomal segments. Molecular polymorphism analysis was performed to determine the parental origin of the abnormality. Methylation and northern blot analyses of the<jats:italic>SNRPN<\/jats:italic> gene were performed to determine the effect of extra copies of the <jats:italic>SNRPN<\/jats:italic> gene on its methylation pattern and expression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Fluorescence in situ hybridisation (FISH) using probes within and flanking the Prader-Willi\/Angelman syndrome critical region indicated that all patients carried an intrachromosomal triplication of proximal 15q11-q14 in one of the two chromosome 15 homologues (trip(15)). In all patients the orientation of the triplicated segments was normal-inverted-normal, suggesting that a common mechanism of rearrangement may have been involved. Microsatellite analysis showed the parental origin of the trip(15) to be maternal in three cases and paternal in one case. The paternal triplication patient had features similar to PWS, one maternal triplication patient had features similar to AS, and the other two maternal triplication patients had non-specific findings including hypotonia and mental retardation. Methylation analysis at exon 1 of the<jats:italic>SNRPN<\/jats:italic> locus showed increased dosage of either the paternal or maternal bands in the paternal or maternal triplication patients, respectively, suggesting that the methylation pattern shows a dose dependent increase that correlates with the parental origin of the triplication. In addition, the expression of<jats:italic>SNRPN<\/jats:italic> was analysed by northern blotting and expression levels were consistent with dosage and parental origin of the triplication.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>These four additional cases of trip(15) will provide additional information towards understanding the phenotypic effects of this abnormality and aid in understanding the mechanism of formation of other chromosome 15 rearrangements.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.38.1.26","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T06:38:40Z","timestamp":1027751920000},"page":"26-34","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":69,"title":["Molecular characterisation of four cases of intrachromosomal triplication of chromosome 15q11-q14"],"prefix":"10.1136","volume":"38","author":[{"given":"Paola","family":"Ungaro","sequence":"first","affiliation":[{"name":"aDepartment of Human Genetics, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA, \n\nbDepartment of Psychiatry, University of Chicago, Chicago, IL, USA, \n\ncGenetics Unit, Department of Anatomy, Chulalongkorn University, Bangkok, Thailand, \n\ndGenetics & IVF Institute, Fairfax, Virginia, USA, \n\neShodair Hospital, Helena, Montana, USA, \n\nfClinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan L","family":"Christian","sequence":"additional","affiliation":[{"name":"aDepartment of Human Genetics, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA, \n\nbDepartment of Psychiatry, University of Chicago, Chicago, IL, USA, \n\ncGenetics Unit, Department of Anatomy, Chulalongkorn University, Bangkok, Thailand, \n\ndGenetics & IVF Institute, Fairfax, Virginia, USA, \n\neShodair Hospital, Helena, Montana, USA, \n\nfClinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judy A","family":"Fantes","sequence":"additional","affiliation":[{"name":"aDepartment of Human Genetics, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA, \n\nbDepartment of Psychiatry, University of Chicago, Chicago, IL, USA, \n\ncGenetics Unit, Department of Anatomy, Chulalongkorn University, Bangkok, Thailand, \n\ndGenetics & IVF Institute, Fairfax, Virginia, USA, \n\neShodair Hospital, Helena, Montana, USA, \n\nfClinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Apiwat","family":"Mutirangura","sequence":"additional","affiliation":[{"name":"aDepartment of Human Genetics, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA, \n\nbDepartment of Psychiatry, University of Chicago, Chicago, IL, USA, \n\ncGenetics Unit, Department of Anatomy, Chulalongkorn University, Bangkok, Thailand, \n\ndGenetics & IVF Institute, Fairfax, Virginia, USA, \n\neShodair Hospital, Helena, Montana, USA, \n\nfClinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Black","sequence":"additional","affiliation":[{"name":"aDepartment of Human Genetics, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA, \n\nbDepartment of Psychiatry, University of Chicago, Chicago, IL, USA, \n\ncGenetics Unit, Department of Anatomy, Chulalongkorn University, Bangkok, Thailand, \n\ndGenetics & IVF Institute, Fairfax, Virginia, USA, \n\neShodair Hospital, Helena, Montana, USA, \n\nfClinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Reynolds","sequence":"additional","affiliation":[{"name":"aDepartment of Human Genetics, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA, \n\nbDepartment of Psychiatry, University of Chicago, Chicago, IL, USA, \n\ncGenetics Unit, Department of Anatomy, Chulalongkorn University, Bangkok, Thailand, \n\ndGenetics & IVF Institute, Fairfax, Virginia, USA, \n\neShodair Hospital, Helena, Montana, USA, \n\nfClinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sue","family":"Malcolm","sequence":"additional","affiliation":[{"name":"aDepartment of Human Genetics, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA, \n\nbDepartment of Psychiatry, University of Chicago, Chicago, IL, USA, \n\ncGenetics Unit, Department of Anatomy, Chulalongkorn University, Bangkok, Thailand, \n\ndGenetics & IVF Institute, Fairfax, Virginia, USA, \n\neShodair Hospital, Helena, Montana, USA, \n\nfClinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William B","family":"Dobyns","sequence":"additional","affiliation":[{"name":"aDepartment of Human Genetics, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA, \n\nbDepartment of Psychiatry, University of Chicago, Chicago, IL, USA, \n\ncGenetics Unit, Department of Anatomy, Chulalongkorn University, Bangkok, Thailand, \n\ndGenetics & IVF Institute, Fairfax, Virginia, USA, \n\neShodair Hospital, Helena, Montana, USA, \n\nfClinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H","family":"Ledbetter","sequence":"additional","affiliation":[{"name":"aDepartment of Human Genetics, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA, \n\nbDepartment of Psychiatry, University of Chicago, Chicago, IL, USA, \n\ncGenetics Unit, Department of Anatomy, Chulalongkorn University, Bangkok, Thailand, \n\ndGenetics & IVF Institute, Fairfax, Virginia, USA, \n\neShodair Hospital, Helena, Montana, USA, \n\nfClinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2001,1,1]]},"reference":[{"key":"2025100521024315000_38.1.26.1","unstructured":"Ledbetter D Ballabio A (1995) molecular cytogenetics of contiguous gene syndromes: mechanism and consequences of gene dosage imbalance. in The metabolic and molecular bases of inherited disease. eds Scriver CR Beaudet AL Sly WS Valle D (McGraw-Hill, New York), pp 811\u2013839."},{"key":"2025100521024315000_38.1.26.2","doi-asserted-by":"publisher","DOI":"10.1086\/301624"},{"key":"2025100521024315000_38.1.26.3","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19960329)62:3<205::AID-AJMG1>3.0.CO;2-S"},{"key":"2025100521024315000_38.1.26.4","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.31.10.798"},{"key":"2025100521024315000_38.1.26.5","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.35.5.425"},{"key":"2025100521024315000_38.1.26.6","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.33.10.848"},{"key":"2025100521024315000_38.1.26.7","first-page":"574","article-title":"Angelman syndrome associated with an inversion of chromosome 15q11.2q24.3.","volume":"60","author":"Greger","year":"1997","journal-title":"Am J Hum 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