"What Does It Mean?": Uncertainties in Understanding Results of Chromosomal Microarray Testing

Overview

Journal Genet Med

Publisher Elsevier

Specialty Genetics

Date 2012 Jan 14

PMID 22241091

Citations 56

Authors

Marian Reiff

Barbara A Bernhardt

Surabhi Mulchandani

Danielle Soucier

Diana Cornell

Reed E Pyeritz

Nancy B Spinner

Affiliations

Soon will be listed here.

Abstract

Purpose: The increased sensitivity of chromosomal microarray (CMA) technology as compared with traditional cytogenetic analysis allows for improved detection of genomic alterations. However, there is potential for uncertainty in the interpretation of test results in some cases. This paper explores how families understand and make meaning of CMA test results, and identifies the needs of families undergoing CMA testing.

Methods: We conducted semistructured interviews with parents of 25 pediatric outpatients with CMA test results indicating either a pathogenic alteration or a variant of unknown significance (VUS). Interviews were analyzed qualitatively.

Results: Three domains of understanding were identified: comprehension of results, interpretations of scientific uncertainty, and personal meaning for the child and family. Incomplete comprehension of test results and scientific uncertainty were prominent themes for families receiving results in both the VUS and pathogenic categories. Receiving results from non-geneticists and by telephone, long waits to see a geneticist, and misleading Internet searches all contributed to misunderstandings.

Conclusion: Differentiating domains of understanding allows for the identification of uncertainties that can be reduced or managed in order to improve understanding of CMA results. Using this framework, we suggest interventions to promote clarity and address the informational needs of families undergoing CMA testing.

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References

Klitzman R . "Am I my genes?": Questions of identity among individuals confronting genetic disease. Genet Med. 2009; 11(12):880-9. PMC: 3667672. DOI: 10.1097/GIM.0b013e3181bfd212. View

Van Riper M . Genetic testing and the family. J Midwifery Womens Health. 2005; 50(3):227-33. DOI: 10.1016/j.jmwh.2005.02.008. View

Lenhard W, Breitenbach E, Ebert H, Schindelhauer-Deutscher H, Henn W . Psychological benefit of diagnostic certainty for mothers of children with disabilities: lessons from Down syndrome. Am J Med Genet A. 2005; 133A(2):170-5. DOI: 10.1002/ajmg.a.30571. View

Timmermans S, Buchbinder M . Patients-in-waiting: Living between sickness and health in the genomics era. J Health Soc Behav. 2010; 51(4):408-23. DOI: 10.1177/0022146510386794. View

Baumanis L, Evans J, Callanan N, Susswein L . Telephoned BRCA1/2 genetic test results: prevalence, practice, and patient satisfaction. J Genet Couns. 2009; 18(5):447-63. DOI: 10.1007/s10897-009-9238-8. View

Fanos J, Gronka S, Wuu J, Stanislaw C, Andersen P, Benatar M . Impact of presymptomatic genetic testing for familial amyotrophic lateral sclerosis. Genet Med. 2011; 13(4):342-8. PMC: 4039017. DOI: 10.1097/GIM.0b013e318204d004. View

Condit C . Public understandings of genetics and health. Clin Genet. 2010; 77(1):1-9. DOI: 10.1111/j.1399-0004.2009.01316.x. View

Biesecker B, Erby L . Adaptation to living with a genetic condition or risk: a mini-review. Clin Genet. 2008; 74(5):401-7. PMC: 2601714. DOI: 10.1111/j.1399-0004.2008.01088.x. View

Makela N, Birch P, Friedman J, Marra C . Parental perceived value of a diagnosis for intellectual disability (ID): a qualitative comparison of families with and without a diagnosis for their child's ID. Am J Med Genet A. 2009; 149A(11):2393-402. DOI: 10.1002/ajmg.a.33050. View

10.

Schaffer R, Kuczynski K, Skinner D . Producing genetic knowledge and citizenship through the Internet: mothers, pediatric genetics, and cybermedicine. Sociol Health Illn. 2008; 30(1):145-59. DOI: 10.1111/j.1467-9566.2007.01042.x. View

11.

Gundersen T . 'One wants to know what a chromosome is': the internet as a coping resource when adjusting to life parenting a child with a rare genetic disorder. Sociol Health Illn. 2010; 33(1):81-95. DOI: 10.1111/j.1467-9566.2010.01277.x. View

12.

Rosenthal E, Biesecker L, Biesecker B . Parental attitudes toward a diagnosis in children with unidentified multiple congenital anomaly syndromes. Am J Med Genet. 2001; 103(2):106-14. DOI: 10.1002/ajmg.1527. View

13.

Baty B, Dudley W, Musters A, Kinney A . Uncertainty in BRCA1 cancer susceptibility testing. Am J Med Genet C Semin Med Genet. 2006; 142C(4):241-50. DOI: 10.1002/ajmg.c.30112. View

14.

Manning M, Hudgins L . Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med. 2010; 12(11):742-5. PMC: 3111046. DOI: 10.1097/GIM.0b013e3181f8baad. View

15.

Kohane I, Masys D, Altman R . The incidentalome: a threat to genomic medicine. JAMA. 2006; 296(2):212-5. DOI: 10.1001/jama.296.2.212. View

16.

Domchek S, Weber B . Genetic variants of uncertain significance: flies in the ointment. J Clin Oncol. 2008; 26(1):16-7. DOI: 10.1200/JCO.2007.14.4154. View

17.

Whitmarsh I, Davis A, Skinner D, Bailey Jr D . A place for genetic uncertainty: parents valuing an unknown in the meaning of disease. Soc Sci Med. 2007; 65(6):1082-93. PMC: 2267724. DOI: 10.1016/j.socscimed.2007.04.034. View

18.

Jackson L, Pyeritz R . Molecular technologies open new clinical genetic vistas. Sci Transl Med. 2011; 3(65):65ps2. DOI: 10.1126/scitranslmed.3002064. View

19.

Mefford H, Sharp A, Baker C, Itsara A, Jiang Z, Buysse K . Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N Engl J Med. 2008; 359(16):1685-99. PMC: 2703742. DOI: 10.1056/NEJMoa0805384. View

20.

Miller D, Adam M, Aradhya S, Biesecker L, Brothman A, Carter N . Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010; 86(5):749-64. PMC: 2869000. DOI: 10.1016/j.ajhg.2010.04.006. View