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Proc Natl Acad Sci U S A. Aug 15, 1995; 92(17): 7612–7616.

Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11.


We report the results of two studies examining the genetic overlap between schizophrenia and velocardiofacial syndrome. In study A, we characterize two interstitial deletions identified on chromosome 22q11 in a sample of schizophrenic patients. The size of the deletions was estimated to be between 1.5 and 2 megabases. In study B, we examine whether variations in deletion size are associated with the schizophrenic phenotype in velocardiofacial syndrome patients. Our results show that a region of the genome that has been previously implicated by genetic linkage analysis can harbor genetic lesions that increase the susceptibility to schizophrenia. Our findings should facilitate identification and cloning of the schizophrenia susceptibility gene(s) in this region and identification of more homogeneous subgroups of patients.

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  • Pulver AE, Karayiorgou M, Wolyniec PS, Lasseter VK, Kasch L, Nestadt G, Antonarakis S, Housman D, Kazazian HH, Meyers D, et al. Sequential strategy to identify a susceptibility gene for schizophrenia: report of potential linkage on chromosome 22q12-q13.1: Part 1. Am J Med Genet. 1994 Mar 15;54(1):36–43. [PubMed]
  • Karayiorgou M, Kasch L, Lasseter VK, Hwang J, Elango R, Bernardini DJ, Kimberland M, Babb R, Francomano CA, Wolyniec PS, et al. Report from the Maryland Epidemiology Schizophrenia Linkage Study: no evidence for linkage between schizophrenia and a number of candidate and other genomic regions using a complex dominant model. Am J Med Genet. 1994 Dec 15;54(4):345–353. [PubMed]
  • Coon H, Jensen S, Holik J, Hoff M, Myles-Worsley M, Reimherr F, Wender P, Waldo M, Freedman R, Leppert M, et al. Genomic scan for genes predisposing to schizophrenia. Am J Med Genet. 1994 Mar 15;54(1):59–71. [PubMed]
  • Lasseter VK, Pulver AE, Wolyniec PS, Nestadt G, Meyers D, Karayiorgou M, Housman D, Antonarakis S, Kazazian H, Kasch L, et al. Follow-up report of potential linkage for schizophrenia on chromosome 22q: Part 3. Am J Med Genet. 1995 Apr 24;60(2):172–173. [PubMed]
  • Pulver AE, Karayiorgou M, Lasseter VK, Wolyniec P, Kasch L, Antonarakis S, Housman D, Kazazian HH, Meyers D, Nestadt G, et al. Follow-up of a report of a potential linkage for schizophrenia on chromosome 22q12-q13.1: Part 2. Am J Med Genet. 1994 Mar 15;54(1):44–50. [PubMed]
  • Scambler PJ, Kelly D, Lindsay E, Williamson R, Goldberg R, Shprintzen R, Wilson DI, Goodship JA, Cross IE, Burn J. Velo-cardio-facial syndrome associated with chromosome 22 deletions encompassing the DiGeorge locus. Lancet. 1992 May 9;339(8802):1138–1139. [PubMed]
  • Golding-Kushner KJ, Weller G, Shprintzen RJ. Velo-cardio-facial syndrome: language and psychological profiles. J Craniofac Genet Dev Biol. 1985;5(3):259–266. [PubMed]
  • Shprintzen RJ, Goldberg R, Golding-Kushner KJ, Marion RW. Late-onset psychosis in the velo-cardio-facial syndrome. Am J Med Genet. 1992 Jan 1;42(1):141–142. [PubMed]
  • Pulver AE, Nestadt G, Goldberg R, Shprintzen RJ, Lamacz M, Wolyniec PS, Morrow B, Karayiorgou M, Antonarakis SE, Housman D, et al. Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives. J Nerv Ment Dis. 1994 Aug;182(8):476–478. [PubMed]
  • Hudson TJ, Colbert AM, Reeve MP, Bae JS, Lee MK, Nussbaum RL, Budarf ML, Emanuel BS, Foote S. Isolation and regional mapping of 110 chromosome 22 STSs. Genomics. 1994 Dec;24(3):588–592. [PubMed]
  • Morrow B, Goldberg R, Carlson C, Das Gupta R, Sirotkin H, Collins J, Dunham I, O'Donnell H, Scambler P, Shprintzen R, et al. Molecular definition of the 22q11 deletions in velo-cardio-facial syndrome. Am J Hum Genet. 1995 Jun;56(6):1391–1403. [PMC free article] [PubMed]
  • Pulver AE, Bale SJ. Availability of schizophrenic patients and their families for genetic linkage studies: findings from the Maryland epidemiology sample. Genet Epidemiol. 1989;6(6):671–680. [PubMed]
  • Lindsay EA, Morris MA, Gos A, Nestadt G, Wolyniec PS, Lasseter VK, Shprintzen R, Antonarakis SE, Baldini A, Pulver AE. Schizophrenia and chromosomal deletions within 22q11.2. Am J Hum Genet. 1995 Jun;56(6):1502–1503. [PMC free article] [PubMed]
  • Driscoll DA, Spinner NB, Budarf ML, McDonald-McGinn DM, Zackai EH, Goldberg RB, Shprintzen RJ, Saal HM, Zonana J, Jones MC, et al. Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome. Am J Med Genet. 1992 Sep 15;44(2):261–268. [PubMed]
  • Halford S, Wadey R, Roberts C, Daw SC, Whiting JA, O'Donnell H, Dunham I, Bentley D, Lindsay E, Baldini A, et al. Isolation of a putative transcriptional regulator from the region of 22q11 deleted in DiGeorge syndrome, Shprintzen syndrome and familial congenital heart disease. Hum Mol Genet. 1993 Dec;2(12):2099–2107. [PubMed]
  • Lindsay EA, Halford S, Wadey R, Scambler PJ, Baldini A. Molecular cytogenetic characterization of the DiGeorge syndrome region using fluorescence in situ hybridization. Genomics. 1993 Aug;17(2):403–407. [PubMed]
  • Driscoll DA, Salvin J, Sellinger B, Budarf ML, McDonald-McGinn DM, Zackai EH, Emanuel BS. Prevalence of 22q11 microdeletions in DiGeorge and velocardiofacial syndromes: implications for genetic counselling and prenatal diagnosis. J Med Genet. 1993 Oct;30(10):813–817. [PMC free article] [PubMed]
  • Weinberger DR. Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry. 1987 Jul;44(7):660–669. [PubMed]
  • Jakob H, Beckmann H. Prenatal developmental disturbances in the limbic allocortex in schizophrenics. J Neural Transm. 1986;65(3-4):303–326. [PubMed]
  • Benes FM, McSparren J, Bird ED, SanGiovanni JP, Vincent SL. Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients. Arch Gen Psychiatry. 1991 Nov;48(11):996–1001. [PubMed]
  • Arnold SE, Hyman BT, Van Hoesen GW, Damasio AR. Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia. Arch Gen Psychiatry. 1991 Jul;48(7):625–632. [PubMed]
  • Akbarian S, Bunney WE, Jr, Potkin SG, Wigal SB, Hagman JO, Sandman CA, Jones EG. Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development. Arch Gen Psychiatry. 1993 Mar;50(3):169–177. [PubMed]
  • Akbarian S, Viñuela A, Kim JJ, Potkin SG, Bunney WE, Jr, Jones EG. Distorted distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in temporal lobe of schizophrenics implies anomalous cortical development. Arch Gen Psychiatry. 1993 Mar;50(3):178–187. [PubMed]

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