Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Aug 15;92(17):7612–7616. doi: 10.1073/pnas.92.17.7612

Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11.

M Karayiorgou 1, M A Morris 1, B Morrow 1, R J Shprintzen 1, R Goldberg 1, J Borrow 1, A Gos 1, G Nestadt 1, P S Wolyniec 1, V K Lasseter 1, et al.
PMCID: PMC41195  PMID: 7644464

Abstract

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.

Full text

PDF
7612

Images in this article

7613Fig. 1
on p.7613

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akbarian S., Bunney W. E., Jr, Potkin S. G., Wigal S. B., Hagman J. O., Sandman C. A., Jones E. G. 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. doi: 10.1001/archpsyc.1993.01820150007001. [DOI] [PubMed] [Google Scholar]
  2. Akbarian S., Viñuela A., Kim J. J., Potkin S. G., Bunney W. E., Jr, Jones E. G. 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. doi: 10.1001/archpsyc.1993.01820150016002. [DOI] [PubMed] [Google Scholar]
  3. Arnold S. E., Hyman B. T., Van Hoesen G. W., Damasio A. R. Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia. Arch Gen Psychiatry. 1991 Jul;48(7):625–632. doi: 10.1001/archpsyc.1991.01810310043008. [DOI] [PubMed] [Google Scholar]
  4. Benes F. M., McSparren J., Bird E. D., SanGiovanni J. P., Vincent S. L. Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients. Arch Gen Psychiatry. 1991 Nov;48(11):996–1001. doi: 10.1001/archpsyc.1991.01810350036005. [DOI] [PubMed] [Google Scholar]
  5. Coon H., Jensen S., Holik J., Hoff M., Myles-Worsley M., Reimherr F., Wender P., Waldo M., Freedman R., Leppert M. Genomic scan for genes predisposing to schizophrenia. Am J Med Genet. 1994 Mar 15;54(1):59–71. doi: 10.1002/ajmg.1320540111. [DOI] [PubMed] [Google Scholar]
  6. Driscoll D. A., Salvin J., Sellinger B., Budarf M. L., McDonald-McGinn D. M., Zackai E. H., Emanuel B. S. 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. doi: 10.1136/jmg.30.10.813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Driscoll D. A., Spinner N. B., Budarf M. L., McDonald-McGinn D. M., Zackai E. H., Goldberg R. B., Shprintzen R. J., Saal H. M., Zonana J., Jones M. C. Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome. Am J Med Genet. 1992 Sep 15;44(2):261–268. doi: 10.1002/ajmg.1320440237. [DOI] [PubMed] [Google Scholar]
  8. Golding-Kushner K. J., Weller G., Shprintzen R. J. Velo-cardio-facial syndrome: language and psychological profiles. J Craniofac Genet Dev Biol. 1985;5(3):259–266. [PubMed] [Google Scholar]
  9. Halford S., Wadey R., Roberts C., Daw S. C., Whiting J. A., O'Donnell H., Dunham I., Bentley D., Lindsay E., Baldini A. 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. doi: 10.1093/hmg/2.12.2099. [DOI] [PubMed] [Google Scholar]
  10. Hudson T. J., Colbert A. M., Reeve M. P., Bae J. S., Lee M. K., Nussbaum R. L., Budarf M. L., Emanuel B. S., Foote S. Isolation and regional mapping of 110 chromosome 22 STSs. Genomics. 1994 Dec;24(3):588–592. doi: 10.1006/geno.1994.1671. [DOI] [PubMed] [Google Scholar]
  11. Jakob H., Beckmann H. Prenatal developmental disturbances in the limbic allocortex in schizophrenics. J Neural Transm. 1986;65(3-4):303–326. doi: 10.1007/BF01249090. [DOI] [PubMed] [Google Scholar]
  12. Karayiorgou M., Kasch L., Lasseter V. K., Hwang J., Elango R., Bernardini D. J., Kimberland M., Babb R., Francomano C. A., Wolyniec P. S. 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. doi: 10.1002/ajmg.1320540413. [DOI] [PubMed] [Google Scholar]
  13. Lasseter V. K., Pulver A. E., Wolyniec P. S., Nestadt G., Meyers D., Karayiorgou M., Housman D., Antonarakis S., Kazazian H., Kasch L. Follow-up report of potential linkage for schizophrenia on chromosome 22q: Part 3. Am J Med Genet. 1995 Apr 24;60(2):172–173. doi: 10.1002/ajmg.1320600217. [DOI] [PubMed] [Google Scholar]
  14. Lindsay E. A., Halford S., Wadey R., Scambler P. J., Baldini A. Molecular cytogenetic characterization of the DiGeorge syndrome region using fluorescence in situ hybridization. Genomics. 1993 Aug;17(2):403–407. doi: 10.1006/geno.1993.1339. [DOI] [PubMed] [Google Scholar]
  15. Lindsay E. A., Morris M. A., Gos A., Nestadt G., Wolyniec P. S., Lasseter V. K., Shprintzen R., Antonarakis S. E., Baldini A., Pulver A. E. Schizophrenia and chromosomal deletions within 22q11.2. Am J Hum Genet. 1995 Jun;56(6):1502–1503. [PMC free article] [PubMed] [Google Scholar]
  16. Morrow B., Goldberg R., Carlson C., Das Gupta R., Sirotkin H., Collins J., Dunham I., O'Donnell H., Scambler P., Shprintzen R. 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] [Google Scholar]
  17. Pulver A. E., Bale S. J. Availability of schizophrenic patients and their families for genetic linkage studies: findings from the Maryland epidemiology sample. Genet Epidemiol. 1989;6(6):671–680. doi: 10.1002/gepi.1370060604. [DOI] [PubMed] [Google Scholar]
  18. Pulver A. E., Karayiorgou M., Lasseter V. K., Wolyniec P., Kasch L., Antonarakis S., Housman D., Kazazian H. H., Meyers D., Nestadt G. 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. doi: 10.1002/ajmg.1320540109. [DOI] [PubMed] [Google Scholar]
  19. Pulver A. E., Karayiorgou M., Wolyniec P. S., Lasseter V. K., Kasch L., Nestadt G., Antonarakis S., Housman D., Kazazian H. H., Meyers D. 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. doi: 10.1002/ajmg.1320540108. [DOI] [PubMed] [Google Scholar]
  20. Pulver A. E., Nestadt G., Goldberg R., Shprintzen R. J., Lamacz M., Wolyniec P. S., Morrow B., Karayiorgou M., Antonarakis S. E., Housman D. Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives. J Nerv Ment Dis. 1994 Aug;182(8):476–478. doi: 10.1097/00005053-199408000-00010. [DOI] [PubMed] [Google Scholar]
  21. Scambler P. J., Kelly D., Lindsay E., Williamson R., Goldberg R., Shprintzen R., Wilson D. I., Goodship J. A., Cross I. E., Burn J. Velo-cardio-facial syndrome associated with chromosome 22 deletions encompassing the DiGeorge locus. Lancet. 1992 May 9;339(8802):1138–1139. doi: 10.1016/0140-6736(92)90734-k. [DOI] [PubMed] [Google Scholar]
  22. Shprintzen R. J., Goldberg R., Golding-Kushner K. J., Marion R. W. Late-onset psychosis in the velo-cardio-facial syndrome. Am J Med Genet. 1992 Jan 1;42(1):141–142. doi: 10.1002/ajmg.1320420131. [DOI] [PubMed] [Google Scholar]
  23. Weinberger D. R. Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry. 1987 Jul;44(7):660–669. doi: 10.1001/archpsyc.1987.01800190080012. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES