Journal of Genetic Counseling

, Volume 23, Issue 6, pp 922–927 | Cite as

Clinical Utility of Chromosomal Microarray Analysis of DNA from Buccal Cells: Detection of Mosaicism in Three Patients

  • Mallory R. Sdano
  • Rena J. Vanzo
  • Megan M. Martin
  • Erin E. Baldwin
  • Sarah T. South
  • Alan F. Rope
  • William P. Allen
  • Hutton Kearney
Case Presentation
First Online:
Received:
Accepted:

Abstract

Mosaic chromosomal abnormalities are relatively common. However, mosaicism may be missed due to multiple factors including failure to recognize clinical indications and order appropriate testing, technical limitations of diagnostic assays, or sampling tissue (s) in which mosaicism is either not present, or present at very low levels. Blood leukocytes have long been the “gold standard” sample for cytogenetic analysis; however, the culturing process for routine chromosome analysis can complicate detection of mosaicism since the normal cell line may have a growth advantage in culture, or may not be present in the cells that produce metaphases (the lymphocytes). Buccal cells are becoming increasingly utilized for clinical analyses and are proving to have many advantages. Buccal swabs allow for simple and noninvasive DNA collection. When coupled with a chromosomal microarray that contains single nucleotide polymorphic probes, analysis of buccal cells can maximize a clinician’s opportunity to detect cytogenetic mosaicism. We present three cases of improved diagnosis of mosaic aberrations using buccal specimens for chromosomal microarray analysis. In each case, the aberration was either undetectable in blood or present at such a low level it likely could have gone undetected. These cases highlight the limitations of certain laboratory methodologies for identifying mosaicism. We also present practice implications for genetic counselors, including clinic workflow changes and counseling approaches based on increasing use of buccal samples.

Keywords

Buccal Microarray CMA Mosaicism Mosaic trisomy 21 Tissue-specific mosaicism Turner syndrome Pallister-Killian syndrome 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgements

The authors sincerely thank the families, the ordering healthcare providers, and staff at ARUP Laboratories, Fullerton Genetics Center, and Lineagen, Inc.

Conflict of Interest

All authors declare that there are no conflicts of interest with this work. However, the authors acknowledge that a potential conflict of interest could exist because Lineagen, Inc, is a for-profit genetic testing company that offers CMA using buccal swabs. ARUP Laboratories and Fullerton Genetics Center are non-profit genetic testing companies that also offer CMA using buccal swabs.

Institutional Review Board (IRB) Approval

The University of Utah IRB does not require review of case reports which do not meet the definition of human subject research. The IRB’s policy on this matter reads:

“In many instances, case reports do involve a human subject (s) by definition, and may contribute to generalized knowledge by presentation or publication. A case report (3 or fewer patients) generally does not meet the definition of a systematic investigation. A case report describes an interesting treatment, presentation or outcome. A critical component is that nothing was done to the patient (s) with prior “research” intent.”

Because all of the above criteria were met for this case report, submission for IRB review was not required.

References

  1. Ballif, B. C., Rorem, E. A., Sundin, K., Lincicum, M., Gaskin, S., Coppinger, J., et al. (2006). Detection of Low-Level Mosaicism by Array CGH in Routine Diagnostic Specimens. American Journal of Medical Genetics. Part A, 140A, 2757–2767.CrossRefGoogle Scholar
  2. Beckett, S. M., Laughton, S. J., Pozza, L. D., McCowage, G. B., Marshall, G., Cohn, R. J., Milne, E., & Ashton, L. J. (2008). Buccal swabs and treated cards: methodological considerations for molecular epidemiologic studies examining pediatric populations. American Journal of Epidemiology, 15;167(10), 1260–7.CrossRefGoogle Scholar
  3. Bruno, D. L., White, S. M., Ganesamoorthy, D., Burgess, T., Butler, K., Corrie, S., et al. (2011). Pathogenic aberrations revealed exclusively by single nucleotide polymorphism (SNP) genotyping data in 5000 samples tested by molecular karyotyping. Journal of Medical Genetics, 48(12), 831–9.PubMedCrossRefGoogle Scholar
  4. Cheung, S. W., Shaw, C. A., Scott, D. A., Patel, A., Sahoo, T., Bacino, C. A., et al. (2007). Microarray-based CGH detects chromosomal mosaicism not revealed by conventional cytogenetics. American Journal of Medical Genetics. Part A, 143A, 1679–1686.PubMedCrossRefGoogle Scholar
  5. Conlin, L. K., Kaur, M., Izumi, K., Campbell, L., Wilkens, A., Clark, D., et al. (2010). Utility of SNP arrays in detecting, quantifying, and determining meiotic origin of tetrasomy 12p in blood from individuals with Pallister–Killian syndrome. American Journal of Medical Genetics. Part A, 158A, 3046–3053.CrossRefGoogle Scholar
  6. Datta, A., Picker, J., & Rotenberg, A. (2010). Trisomy 8 mosaicism and favorable outcome after treatment of infantile spasms: case report. Journal of Child Neurology, 25(10), 1275–7.PubMedCrossRefGoogle Scholar
  7. Garnham, I., Fernandez, H., Callen, D. F., Haan, E. A., & Sutherland, G. R. (1994). Discordance between direct and PHA-stimulated chromosome preparations from neonates. Clinical Genetics, 45, 277–280.PubMedCrossRefGoogle Scholar
  8. Hook, E. B. (1977). Exclusion of chromosomal mosaicism: tables of 90 %, 95 % and 99 % confidence limits and comments on use. The American Journal of Human Genetics, 29, 94–97.Google Scholar
  9. Horsman, D. E., Dill, F. J., McGillivray, B. C., & Kalousek, D. K. (1987). X chromosome aneuploidy in lymphocyte cultures from women with recurrent spontaneous abortions. American Journal of Medical Genetics, 28, 981–987.PubMedCrossRefGoogle Scholar
  10. Izumi, K., Conlin, L. K., Berrodin, D., Fincher, C., Wilkens, A., Haldeman-Englert, C., et al. (2012). Duplication 12p and Pallister-Killian syndrome: a case report and review of the literature toward defining a Pallister-Killian syndrome minimal critical region. American Journal of Medical Genetics. Part A, 158A(12), 3033–45.PubMedCrossRefGoogle Scholar
  11. Leon, E., Zou, Y. S., & Milunsky, J. M. (2010). Mosaic Down syndrome in a patient with low-level mosaicism detected by microarray. American Journal of Medical Genetics. Part A, 152A, 3154–3156.PubMedCrossRefGoogle Scholar
  12. Menten, B., Maas, N., Thienpont, B., Buysse, K., Vandesompele, J., Melotte, C., et al. (2006). Emerging patterns of cryptic chromosomal imbalance in patients with idiopathic mental retardation and multiple congenital anomalies: a new series of 140 patients and review of published reports. Journal of Medical Genetics, 43(8), 625–33.PubMedCentralPubMedCrossRefGoogle Scholar
  13. Nedel, F., Conde, M. C., Oliveira, I. O., Tarquinio, S. B., & Demarco, F. F. (2009). Comparison between DNA obtained from buccal cells of the upper and lower gutter area. Brazilian Dental Journal, 20(4), 275–8.17.PubMedCrossRefGoogle Scholar
  14. Peltomäki, P., Knuutila, S., Ritvanen, A., Kaitila, I., & de la Chapelle, A. (1987). Pallister-Killian syndrome: cytogenetic and molecular studies. Clinical Genetics, 31(6), 399–405.PubMedCrossRefGoogle Scholar
  15. Repnikova, E. A., Astbury, C., Reshmi, S. C., Ramsey, S. N., Atkin, J. F., Thrush, D. L., et al. (2012). Microarray comparative genomic hybridization and cytogenetic characterization of tissue-specific mosaicism in three patients. American Journal of Medical Genetics. Part A, 158A, 1924–1933.PubMedCrossRefGoogle Scholar
  16. Theisen, A., Rosenfeld, J. A., Farrell, S. A., Harris, C. J., Wetzel, H. H., Torchia, B. A., et al. (2009). aCGH detects partial tetrasomy of 12p in blood from Pallister–Killian syndrome cases without invasive skin biopsy. American Journal of Medical Genetics. Part A, 149A, 914–918.PubMedCrossRefGoogle Scholar

Copyright information

© National Society of Genetic Counselors, Inc. 2014

Authors and Affiliations

  • Mallory R. Sdano
    • 1
  • Rena J. Vanzo
    • 1
  • Megan M. Martin
    • 1
  • Erin E. Baldwin
    • 2
  • Sarah T. South
    • 2
    • 3
    • 4
  • Alan F. Rope
    • 5
  • William P. Allen
    • 6
  • Hutton Kearney
    • 7
  1. 1.Genetic Counselor, Lineagen, IncWay Salt Lake CityUSA
  2. 2.ARUP LaboratoriesSalt Lake CityUSA
  3. 3.Department of PathologyUniversity of UtahSalt Lake CityUSA
  4. 4.Department of PediatricsUniversity of UtahSalt Lake CityUSA
  5. 5.Department of Medical Genetics Northwest Kaiser PermanentePortlandUSA
  6. 6.Fullerton Genetics CenterMission HealthAshevilleUSA
  7. 7.Department of Laboratory Medicine and Pathology Mayo ClinicRochesterUSA

Personalised recommendations