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Am J Hum Genet. Oct 1994; 55(4): 753–759.
PMCID: PMC1918309

Cytogenetic and molecular characterization of inverted duplicated chromosomes 15 from 11 patients.


We have studied the inverted duplicated chromosomes 15 (inv dup(15)) from 11 individuals--7 with severe mental retardation and seizures, 3 with a normal phenotype, and 1 with Prader-Willi syndrome (PWS). Through a combination of FISH and quantitative DNA analyses, three different molecular sizes of inv dup(15) were identified. The smallest inv dup(15) was positive only for the centromeric locus D15Z1 (type 1); the next size was positive for D15Z1 and D15S18 (type 2); and the largest inv dup(15) was positive for two additional copies of loci extending from D15Z1 and D15S18 through D15S12 (type 3). Type 1 or type 2 was observed in the three normal individuals and the PWS patient. Type 3 was observed in all seven individuals with mental retardation and seizures but without PWS or Angelman Syndrome (AS). The PWS patient, in addition to being mosaic for a small inv dup(15), demonstrated at D15S63 a methylation pattern consistent with maternal uniparental inheritance of the normal chromosomes 15. The results from this study show (a) two additional copies of proximal 15q loci, D15S9 through D15S12, in mentally retarded patients with an inv dup(15) but without AS or PWS and (b) no additional copies of these loci in patients with a normal phenotype or with PWS.

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  • Buckton KE, Spowart G, Newton MS, Evans HJ. Forty four probands with an additional "marker" chromosome. Hum Genet. 1985;69(4):353–370. [PubMed]
  • Butler MG, Palmer CG. Parental origin of chromosome 15 deletion in Prader-Willi syndrome. Lancet. 1983 Jun 4;1(8336):1285–1286. [PubMed]
  • Dittrich B, Robinson WP, Knoblauch H, Buiting K, Schmidt K, Gillessen-Kaesbach G, Horsthemke B. Molecular diagnosis of the Prader-Willi and Angelman syndromes by detection of parent-of-origin specific DNA methylation in 15q11-13. Hum Genet. 1992 Nov;90(3):313–315. [PubMed]
  • Donlon TA, Lalande M, Wyman A, Bruns G, Latt SA. Isolation of molecular probes associated with the chromosome 15 instability in the Prader-Willi syndrome. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4408–4412. [PMC free article] [PubMed]
  • Freeman SB, May KM, Pettay D, Fernhoff PM, Hassold TJ. Paternal uniparental disomy in a child with a balanced 15;15 translocation and Angelman syndrome. Am J Med Genet. 1993 Mar 1;45(5):625–630. [PubMed]
  • Hamabe J, Fukushima Y, Harada N, Abe K, Matsuo N, Nagai T, Yoshioka A, Tonoki H, Tsukino R, Niikawa N. Molecular study of the Prader-Willi syndrome: deletion, RFLP, and phenotype analyses of 50 patients. Am J Med Genet. 1991 Oct 1;41(1):54–63. [PubMed]
  • Hamabe J, Kuroki Y, Imaizumi K, Sugimoto T, Fukushima Y, Yamaguchi A, Izumikawa Y, Niikawa N. DNA deletion and its parental origin in Angelman syndrome patients. Am J Med Genet. 1991 Oct 1;41(1):64–68. [PubMed]
  • Knight LA, Lipson M, Mann J, Bachman R. Mosaic inversion duplication of chromosome 15 without phenotypic effect: occurrence in a father and daughter. Am J Med Genet. 1984 Mar;17(3):649–654. [PubMed]
  • Knoll JH, Nicholls RD, Magenis RE, Glatt K, Graham JM, Jr, Kaplan L, Lalande M. Angelman syndrome: three molecular classes identified with chromosome 15q11q13-specific DNA markers. Am J Hum Genet. 1990 Jul;47(1):149–154. [PMC free article] [PubMed]
  • Knoll JH, Nicholls RD, Magenis RE, Graham JM, Jr, Lalande M, Latt SA. Angelman and Prader-Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletion. Am J Med Genet. 1989 Feb;32(2):285–290. [PubMed]
  • Knoll JH, Sinnett D, Wagstaff J, Glatt K, Wilcox AS, Whiting PM, Wingrove P, Sikela JM, Lalande M. FISH ordering of reference markers and of the gene for the alpha 5 subunit of the gamma-aminobutyric acid receptor (GABRA5) within the Angelman and Prader-Willi syndrome chromosomal regions. Hum Mol Genet. 1993 Feb;2(2):183–189. [PubMed]
  • Kuwano A, Mutirangura A, Dittrich B, Buiting K, Horsthemke B, Saitoh S, Niikawa N, Ledbetter SA, Greenberg F, Chinault AC, et al. Molecular dissection of the Prader-Willi/Angelman syndrome region (15q11-13) by YAC cloning and FISH analysis. Hum Mol Genet. 1992 Sep;1(6):417–425. [PubMed]
  • Lalande M, Dryja TP, Schreck RR, Shipley J, Flint A, Latt SA. Isolation of human chromosome 13-specific DNA sequences cloned from flow sorted chromosomes and potentially linked to the retinoblastoma locus. Cancer Genet Cytogenet. 1984 Dec;13(4):283–295. [PubMed]
  • Lawrence JB, Singer RH, McNeil JA. Interphase and metaphase resolution of different distances within the human dystrophin gene. Science. 1990 Aug 24;249(4971):928–932. [PubMed]
  • Lazarus AL, Moore KE, Spinner NB. Recurrent neuroleptic malignant syndrome associated with inv dup(15) and mental retardation. Clin Genet. 1991 Jan;39(1):65–67. [PubMed]
  • Leana-Cox J, Jenkins L, Palmer CG, Plattner R, Sheppard L, Flejter WL, Zackowski J, Tsien F, Schwartz S. Molecular cytogenetic analysis of inv dup(15) chromosomes, using probes specific for the Prader-Willi/Angelman syndrome region: clinical implications. Am J Hum Genet. 1994 May;54(5):748–756. [PMC free article] [PubMed]
  • Ledbetter DH, Mascarello JT, Riccardi VM, Harper VD, Airhart SD, Strobel RJ. Chromosome 15 abnormalities and the Prader-Willi syndrome: a follow-up report of 40 cases. Am J Hum Genet. 1982 Mar;34(2):278–285. [PMC free article] [PubMed]
  • Malcolm S, Clayton-Smith J, Nichols M, Robb S, Webb T, Armour JA, Jeffreys AJ, Pembrey ME. Uniparental paternal disomy in Angelman's syndrome. Lancet. 1991 Mar 23;337(8743):694–697. [PubMed]
  • Maraschio P, Zuffardi O, Bernardi F, Bozzola M, De Paoli C, Fonatsch C, Flatz SD, Ghersini L, Gimelli G, Loi M, et al. Preferential maternal derivation in inv dup(15): analysis of eight new cases. Hum Genet. 1981;57(4):345–350. [PubMed]
  • Mascari MJ, Gottlieb W, Rogan PK, Butler MG, Waller DA, Armour JA, Jeffreys AJ, Ladda RL, Nicholls RD. The frequency of uniparental disomy in Prader-Willi syndrome. Implications for molecular diagnosis. N Engl J Med. 1992 Jun 11;326(24):1599–1607. [PubMed]
  • Mattei MG, Souiah N, Mattei JF. Chromosome 15 anomalies and the Prader-Willi syndrome: cytogenetic analysis. Hum Genet. 1984;66(4):313–334. [PubMed]
  • Nicholls RD, Knoll JH, Butler MG, Karam S, Lalande M. Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome. Nature. 1989 Nov 16;342(6247):281–285. [PubMed]
  • Nicholls RD, Knoll JH, Glatt K, Hersh JH, Brewster TD, Graham JM, Jr, Wurster-Hill D, Wharton R, Latt SA. Restriction fragment length polymorphisms within proximal 15q and their use in molecular cytogenetics and the Prader-Willi syndrome. Am J Med Genet. 1989 May;33(1):66–77. [PubMed]
  • Robinson WP, Binkert F, Giné R, Vazquez C, Müller W, Rosenkranz W, Schinzel A. Clinical and molecular analysis of five inv dup(15) patients. Eur J Hum Genet. 1993;1(1):37–50. [PubMed]
  • Robinson WP, Bottani A, Xie YG, Balakrishman J, Binkert F, Mächler M, Prader A, Schinzel A. Molecular, cytogenetic, and clinical investigations of Prader-Willi syndrome patients. Am J Hum Genet. 1991 Dec;49(6):1219–1234. [PMC free article] [PubMed]
  • Robinson WP, Wagstaff J, Bernasconi F, Baccichetti C, Artifoni L, Franzoni E, Suslak L, Shih LY, Aviv H, Schinzel AA. Uniparental disomy explains the occurrence of the Angelman or Prader-Willi syndrome in patients with an additional small inv dup(15) chromosome. J Med Genet. 1993 Sep;30(9):756–760. [PMC free article] [PubMed]
  • Sachs ES, Van Hemel JO, Den Hollander JC, Jahoda MG. Marker chromosomes in a series of 10,000 prenatal diagnoses. Cytogenetic and follow-up studies. Prenat Diagn. 1987 Feb;7(2):81–89. [PubMed]
  • Schreck RR, Breg WR, Erlanger BF, Miller OJ. Preferential derivation of abnormal human G-group-like chromosomes from chromosome 15. Hum Genet. 1977 Apr 7;36(1):1–12. [PubMed]
  • Seabright M. A rapid banding technique for human chromosomes. Lancet. 1971 Oct 30;2(7731):971–972. [PubMed]
  • Shibuya Y, Tonoki H, Kajii N, Niikawa N. Identification of a marker chromosome as inv dup(15) by molecular analysis. Clin Genet. 1991 Sep;40(3):233–236. [PubMed]
  • Stetten G, Sroka-Zaczek B, Corson VL. Prenatal detection of an accessory chromosome identified as an inversion duplication (15). Hum Genet. 1981;57(4):357–359. [PubMed]
  • Wagstaff J, Knoll JH, Fleming J, Kirkness EF, Martin-Gallardo A, Greenberg F, Graham JM, Jr, Menninger J, Ward D, Venter JC, et al. Localization of the gene encoding the GABAA receptor beta 3 subunit to the Angelman/Prader-Willi region of human chromosome 15. Am J Hum Genet. 1991 Aug;49(2):330–337. [PMC free article] [PubMed]
  • Wisniewski L, Hassold T, Heffelfinger J, Higgins JV. Cytogenetic and clinical studies in five cases of inv dup(15). Hum Genet. 1979 Sep;50(3):259–270. [PubMed]
  • Yunis JJ. High resolution of human chromosomes. Science. 1976 Mar 26;191(4233):1268–1270. [PubMed]

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