Skip to main content
SpringerLink
Log in

Microdeletion Syndromes

Characteristics and Diagnosis

  • Protocol
Molecular Cytogenetics

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 204))

Abstract

Schmickel first defined the Contiguous Gene syndromes in 1986. These are syndromes that involve the deletion of a contiguous stretch of DNA, including multiple genes, on a chromosome. They are also referred to as microdeletion syndromes or segmental aneusomy. These syndromes are clinically recognized with distinct physical, behavioral, and mental characteristics and often involve some individual features that can be inherited in a Mendelian fashion (i.e., lissencephaly, heart defects, etc.). No other type of cytogenetic abnormality has benefited more from the introduction of fluorescence in situ hybridization (FISH) than these syndromes. While some of the abnormalities can be detected cytogenetically, FISH has added dramatically to the detection of these disorders and should be used whenever possible to confirm the deletions (Table 1).

Table 1 Microdeletion Syndromes
Full size table

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Juyal R. C., Figuera F. L., Hauge F. L., Elsea S. H., Lupski J. R., Greenberg F., et al. (1996) Molecular analyses of 17p11.2 deletions in 62 Smith-Magenis syndrome patients. Am. J. Hum. Genet. 58, 998–1007.

    CAS  PubMed  Google Scholar 

  2. Chong S. S., Pack S. D., Roschke A. V., Tanigami A., Carrozzo R., Smith A. C., et al. (1997) A revision of the lissencephaly and Miller-Dieker syndrome critical regions in chromosome 17p13.3. Hum. Mol. Genet. 6, 147–155.

    Article  CAS  PubMed  Google Scholar 

  3. Cassidy S. B. and Schwartz S. (1998) Prader-Willi and Angelman syndromes. Disorders of genomic imprinting. Medicine (Baltimore) 77, 140–151.

    Article  CAS  Google Scholar 

  4. Funke B., Edelmann L., McCain N., Pandita R. K., Ferreira J., Merscher S., et al. (1999) Der(22) and velo-cardio-facial syndrome/DiGeorge syndrome share a 1.5 Mb region of overlap on chromosome 22q11. Am. J. Hum. Genet. 64, 747–758.

    Article  CAS  PubMed  Google Scholar 

  5. Brondum-Nielsen K., Beck B., Gyftodimou J., Horlyk H., Liljenberg U., Pedersen M. B., et al. (1997) Investigation of deletions at 7q11.23 in 44 patients referred for Williams-Beuren syndrome, using FISH and four DNA polymorphisms. Hum. Genet. 99, 56–61.

    Article  CAS  PubMed  Google Scholar 

  6. Elcioglu N., Mackie-Ogilvie C., Daker M., and Berry A. C. (1998) FISH analysis in patients with clinical diagnosis of Williams syndrome. Acta Paediatr. 87, 48–53.

    Article  CAS  PubMed  Google Scholar 

  7. Meng X., Lu X., Li Z., Green E. D., Massa H., Trask B. J., et al. (1998) Complete physical map of the common deletion region in Williams syndrome and identification and characterization of three novel genes. Hum. Genet. 103, 590–599.

    Article  CAS  PubMed  Google Scholar 

  8. Wu Y. Q., Sutton V. R., Nickerson E., Lupski J. R., Potocki L., Korenberg J. R., et al. (1998) Delineation of the common critical region in Williams syndrome and clinical correlation of growth, heart defects, ethnicity, and parental origin. Am. J. Med. Genet. 78, 82–89.

    Article  CAS  PubMed  Google Scholar 

  9. Ludecke J. J., Schmidt O., Nardmann J., von Holtum D., Meinecke P., Muenke M., et al. (1999) Genes and chromosomal breakpoints in the Langer-Giedion syndrome region on human chromosome 8. Hum. Genet. 105, 619–628.

    Article  CAS  PubMed  Google Scholar 

  10. Hou J., Parrish J., Ludecke H. J., Sapru M., Want Y., Chen W., et al. (1995) A 4-megabaseYAC contig that spans the Langer-Giedion syndrome region on human chromosome 8q24.1: use in refining the location of the trichorhinophalangeal syndrome and multiple exostoses genes (TRPS1 and EXT1). Genomics 29, 87–97.

    Article  CAS  PubMed  Google Scholar 

  11. Taine L., Goizet C., Wen Z. Q., Petrij F., Bruening M. H., Ayme S., et al. (1998) Submicroscopic deletion of chromosome 16p13.3 in patients with Rubinstein-Taybi syndrome. Am. J. Med. Genet. 78, 267–270.

    Article  CAS  PubMed  Google Scholar 

  12. Petrij F., Dauwerse H. G., Blough R. I., Giles R. H., van der Smagt J. J., Wallerstein, R., et al. (2000) Diagnostic analysis of the Rubinstein-Taybi syndrome: five cosmids should be used for microdeletion detection and low number of protein truncating mutations. J. Med. Genet. 37, 168–176.

    Article  CAS  PubMed  Google Scholar 

  13. Bartsch O., Wagner A., Hinkel G. K., Krebs P., Stumm M., Schmalenberger B., et al. (1999) FISH studies in 45 patients with Rubinstein-Taybi syndrome: deletions associated with polysplenia, hypoplastic left heart and death in infancy, Eur. J. Hum. Genet. 7, 748–756.

    Article  CAS  Google Scholar 

  14. Mannens M., Hoovers J. M., Bleeck-Wagemakers E. M., Redeker E., Bliek J., Overbeeke-Melkert M., et al. (1991) The distal region of 11p13 and associated genetic diseases. Genomics 11, 284–293.

    Article  CAS  PubMed  Google Scholar 

  15. Crolla J. A., Cawdery J. E., Oley C. A., Young I. D., Gray J., Hantes J., et al. (1997) A FISH approach to defining the extent and possible clinical significance of deletions at the WAGR locus. J. Med. Genet. 34, 207–212.

    Article  CAS  PubMed  Google Scholar 

  16. Lamb J., Harris P. C., Wilkie A. O., Wood W. G., Dauwerse J. G., and Higgs D. R. (1993) De novo truncation of chromosome 16p and healing with (TTAGGG)n in the alphathalassemia/ mental retardation syndrome (ATR-16). Am. J. Hum. Genet. 52, 668–676.

    CAS  PubMed  Google Scholar 

  17. Pfeifer D., Poulat F., Holinski-Feder E., Kooy F., and Scherer G. (2000) The SOX8 gene is located within 700 kb of the tip of chromosome 16p and is deleted in a patient with ATR-16 syndrome Genomics 63, 108–116.

    Article  CAS  PubMed  Google Scholar 

  18. Krantz I. D., Piccoli D. A., and Spinner N. B. (1999) Clinical and molecular genetics of Alagille syndrome. Curr. Opin. Pediatr. 11, 558–564.

    Article  CAS  PubMed  Google Scholar 

  19. Krantz I. D., Colliton R. P., Genin A., Rand E. B., Li L., Piccoli, et al. (1998) Spectrum and frequency of jagged1 (JAG1) mutations in Alagille syndrome patients and their families. Am. J. Hum. Genet. 62, 1361–1369.

    Article  CAS  PubMed  Google Scholar 

  20. Krantz I. D., Smith R., Colliton R. P., Tinkel H., Zackai E. H., Piccoli D. A., et al. (1999) Jagged1 mutations in patients ascertained with isolated congenital heart defects. Am. J. Hum. Genet. 84, 56–60.

    CAS  Google Scholar 

  21. Kalff-Suske M., Wild A., Topp J., Wessling M., Jacobsen E. M., Bornholt D., et al. (1999) Point mutations throughout the GLI13 gene causing Grieg cephalopolysyndactyly syndrome. Hum. Mol. Genet. 8, 1769–1777.

    Article  CAS  PubMed  Google Scholar 

  22. Williams P. G., Hersh J. H., Yen F. F., Barch M. J., Kleinert H. E., Kunz J., et al. (1997) Greig cephalopolysyndactyly syndrome: altered phenotype of a microdeletion syndrome due to the presence of a cytogenetic abnormality. Clin. Genet. 52, 436–441.

    Article  CAS  PubMed  Google Scholar 

  23. Phelan M. C., Rogers R. C., Clarkson K. B., Bowyer F. P., Levine M. A., Estabrooks L. L., et al. (1995) Albright hereditary osteodystrophy and del(2) (q37.3) in four unrelated individuals. Am. J. Hum. Genet. 58, 1–7.

    CAS  Google Scholar 

  24. Wilson L. C., Leverton K., Oudi Luttikhuis M. E., Oley C. A., Flint J., Wolstenholme J., et al. (1995) Brachydactyly and mental retardation: an Albright hereditary osteodystrophylike syndrome localized to 2q37. Am. J. Hum. Genet. 56, 400–407.

    CAS  PubMed  Google Scholar 

  25. Slavotinek A., Shaffer L. G., and Shapira S. K. (1999) Monosomy 1p36. J. Med. Genet. 36, 657–663.

    CAS  PubMed  Google Scholar 

  26. Knight-Jones E., Knight S., Heussler H., Regan R., Flint J., and Martin K. (2000) Neurodevelopmental profile of a new dysmorphic syndrome associated with submicroscopic partial deletion of 1p36.3. Dev. Med. Child. Neurol. 42, 201–206.

    Article  CAS  PubMed  Google Scholar 

  27. Shapira S. K., McCaskill C., Northrup H., Sikes A. S., Elder F. F., Sutton V. R., et al. (1997) Chromosome 1p36 deletions: the clinical phenotype and molecular characterization of a common newly delineated syndrome. Am. J. Hum. Genet. 61, 642–650.

    Article  CAS  PubMed  Google Scholar 

  28. Gohlke B. C., Haug K., Funkami M., Friedl W., Noeker M., Rappold G. A., et al. (2000) Interstitial deletion in Xp22.3 is associated with X linked ichthyosis, mental retardation, and epilepsy. J. Med. Genet. 37, 600–602.

    Article  CAS  PubMed  Google Scholar 

  29. Weissortel R., Strom T. M., Dorr H. G., Rauch A., and Meitinger T. (1998) Analysis of an interstitial deletion in a patient with Kallmann syndrome, X-linked ichthyosis and mental retardation. Clin. Genet. 54, 45–51.

    Article  CAS  PubMed  Google Scholar 

  30. Fries M. H., Lebo R. V., Schonberg S. A., Golabi M., Seltzer W. K., Gitelman S. E., et al. (1993) Mental retardation locus in Xp21 chromosome microdeletion. Am. J. Hum. Genet. 46, 363–368.

    CAS  Google Scholar 

  31. Stuhrmann M., Heilbronner H., Reis A., Wegner R. D., Fischer P., and Schmidtke J. (1991) Characterisation of a Xp21 microdeletion syndrome in a 2-year-old boy with muscular dystrop, glycerol kinase deficiency and adrenal hypoplasia congenita. Hum. Genet. 86, 414–415.

    Article  CAS  PubMed  Google Scholar 

  32. Gripp K. W., Zackai E. H., and Stolle C. A. (2000) Mutations in the human TWIST gene. Hum. Mutat. 15, 150–155.

    Article  CAS  PubMed  Google Scholar 

  33. Johnson D., Horsley S., Moloney D. M., Oldridge M., Twigg S. R., Walsh S., et al. (1998) A comprehensive screen for TWIST mutations in patients with craniosynostosis identifies a new microdeletion syndrome of chromosome band 7p21.1. Am. J. Hum. Genet. 63, 1282–1293.

    Article  CAS  PubMed  Google Scholar 

  34. Schutte B. C., Bjork B. C., Coppage K. B., Malik M. I., Gregory S. G., Scott D. J., et al. (2000) A preliminary gene map for the Van der Woude Syndrome critical region derived from 900 kb of genomic sequence at 1q32-q41. Genome Res. 10, 81–94.

    CAS  PubMed  Google Scholar 

  35. Schutte B. C., Basart A. M., Watanabe Y., Laffin J. J., Coppage K., Bjork B. C., et al. (1999) Microdeletions at chromosome bands 1q32-q41 as a cause of Van der Woude syndrome. Am. J. Hum. Genet. 84, 145–150.

    CAS  Google Scholar 

  36. Tentler D., Gustavsson P., Elinder G., Eklof O., Gordon L., Mandel A., et al. (2000) A microdeletion in 19q13.2 associated with mental retardation, skeletal malformations, and Diamond-Blackfan anaemia suggests a novel contiguous gene syndrome. J. Med. Genet. 37, 128–131.

    Article  CAS  PubMed  Google Scholar 

  37. Gustavsson P., Garelli E., Draptchinskaia N., Ball S., Willig T. N., Tentler D., et al. (1998), Identificatin of microdeletions spanning the Diamond-Blackfan anemia locus on 19q13 and evidence for genetic heterogeneity. Am. J. Hum. Genet. 63, 1388–1395.

    Article  CAS  PubMed  Google Scholar 

  38. Correa C. L., Brems H., Lazaro C., Marynen P., and Legius E. (2000) Unequal Meiotic Crossover: A Frequent Cause of NF1 Microdeletions. Am. J. Hum. Genet. 66, 1969–1974.

    Article  CAS  Google Scholar 

  39. Riva P., Corrado L., Natacci F., Castorina P., Wu B. L., Schneider G. H., et al. (2000) NF1 microdeletion syndrome: refined FISH characterization of sporadic and familial deletions with locus-specific probes. Am. J. Hum. Genet. 66, 100–109.

    Article  CAS  PubMed  Google Scholar 

  40. Praphanphoj V., Goodman K., Thomas G. H., and Raymond G. V. (2000) Cryptic subtelomeric translocations in the 22q13 deletion syndrome. J. Med. Genet. 37, 58–61.

    Article  CAS  PubMed  Google Scholar 

  41. Precht K. K., Lese C. M., Spiro R. P., Huttenlocher P. R., Johnston K. M., Baker J. C., et al. (1998) Two 22q telomere deletions serendipitously detected by FISH. J. Med. Genet. 35, 939–942.

    Article  CAS  PubMed  Google Scholar 

  42. Maurer B., Gromoll J., Simoni M., and Nieschlag E. (2001) Prevalence of Y chromosome microdeletions in infertile men who consulted a tertiary care medical centre: the Munster experience. Andrologia 33, 27–33

    Article  CAS  PubMed  Google Scholar 

  43. Van Landuyt L., Lissens W., Stouffs K., Tournaye H., Liebaers I., and Van Steirteghem, A. (2000) Validation of a simple Yq deletion screening programme in an ICSI candidate population. Mol. Hum. Reprod. 6, 291–297.

    Article  PubMed  Google Scholar 

  44. Potocki L., Chen K. S., Park S. S., Osterholm D. E., Withers M. A., Kimonis V., et al. (2000) Molecular mechanism for duplication 17p11.2-the homologous recombination reciprocal of the Smith-Magenis microdeletion. Eur. J. Hum. Genet. 8, 220–235.

    Google Scholar 

  45. Thomas P. K., Marques W., Jr., Davei M. B., Sweeney M. G., King R. H., Bradley J. L., et al. (1997) The phenotypic manifestations of chromosome 17p11.2 duplication. Brain 120 (Pt3), 465–478.

    Article  PubMed  Google Scholar 

  46. Berends M. J., Tan-Sindhunata G., Leegte B., and van Essen A. J. (2001) Phenotypic variability of Cat-Eye syndrome. Genet. Couns. 12, 23–34.

    CAS  PubMed  Google Scholar 

  47. Johnson A., Minoshima S., Asakawa S., Shimizu N., Shizuya H., Roe B. A., et al. (1999) A 1.5-Mb contig within the cat eye syndrome critical region at human chromosome 22q11.2. Genomics 57, 306–309.

    Article  CAS  PubMed  Google Scholar 

  48. Wandstrat A. E., Leana-Cox J., Jenkins L., and Schwartz S. (1998) Molecular cytogenetic evidence for a common breakpoint in the largest inverted duplications of chromosome 15. Am. J. Hum. Genet. 62, 925–936

    Article  CAS  PubMed  Google Scholar 

  49. Leana-Cox J., Jenkins L., Palmer C. G., Plattner R., Sheppard L., Flejter W. L., et al. (1994) Molecular cytogenetic analysis of inv dup(15) chromosomes, using probes specific for the Prader-Willi/Angelman syndrome region: clinical implications. Am. J. Hum. Genet. 54, 748–756.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Genetics and Center for Human Genetics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH

    Stuart Schwartz

  2. Department of Genetics and Center for Human Genetics Laboratory, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio

    Michael D. Graf

Authors
  1. Stuart Schwartz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael D. Graf
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. London Health Sciences Center, London

    Yao-Shan Fan

  2. The University of Western Ontario, Ontario, Canada

    Yao-Shan Fan

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Humana Press Inc.

About this protocol

Cite this protocol

Schwartz, S., Graf, M.D. (2002). Microdeletion Syndromes. In: Fan, YS. (eds) Molecular Cytogenetics. Methods in Molecular Biology™, vol 204. Humana Press. https://doi.org/10.1385/1-59259-300-3:275

Download citation

  • DOI: https://doi.org/10.1385/1-59259-300-3:275

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-006-9

  • Online ISBN: 978-1-59259-300-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation