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The Paternal Age Effect: a Preliminary Study of Current Challenges for Prenatal Genetics Care

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The Paternal Age Effect: a Preliminary Study of Current Challenges for Prenatal Genetics Care University of South Carolina Scholar Commons Theses and Dissertations 2014 The aP ternal Age Effect: A Preliminary Study of Current Challenges for Prenatal Genetics Care Andrew Tyler Gunter University of South Carolina - Columbia Follow this and additional works at: https://scholarcommons.sc.edu/etd Part of the Genetics and Genomics Commons Recommended Citation Gunter, A. T.(2014). The Paternal Age Effect: A Preliminary Study of Current Challenges for Prenatal Genetics Care. (Master's thesis). Retrieved from https://scholarcommons.sc.edu/etd/2599 This Open Access Thesis is brought to you by Scholar Commons. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of Scholar Commons. For more information, please contact [email protected]. The Paternal Age Effect: A Preliminary Study of Current Challenges for Prenatal Genetics Care by Andrew T. Gunter Bachelor of Science Clemson University, 2011 Bachelor of Arts Clemson University, 2011 Submitted in Partial Fulfillment of the Requirements For the Degree of Master of Science in Genetic Counseling School of Medicine University of South Carolina 2014 Accepted by: Peggy Walker, Director of Thesis Isaac M. Lipkus, Reader Helga V. Toriello, Reader Lacy Ford, Vice Provost and Dean of Graduate Studies © Copyright by Andrew T. Gunter, 2014 All Rights Reserved. ii Dedication This study is dedicated to fathers everywhere. May they love and lead their families well. iii Acknowledgements I first give thanks to my God and Savior, Jesus Christ. As I start my career, my prayer is that I will use these gifts and training for his glory and to make him known. I cannot express enough gratitude to my adviser, Peggy, and to my exceptional committee members, Isaac and Helga, for their time, guidance, and expertise throughout this project. To the faculty of the Genetic Counseling program at USC, thank you for your investment in the future of genetic counseling and for your enthusiasm as you have taught me and earnestly sought to see your passions become my own. To my extraordinary classmates who inspire me each day, thank you for driving me to grow my skills and for your encouragement. I know that each of you will be an asset to your practices and an incredible colleague in the field. Many thanks to my family and friends who have been so encouraging as I begin my career. Thank you for your prayers, phone calls, emails, hospitality, and time over the past two years. Finally, I especially want to thank my parents for exemplifying sacrificial love and support for my entire life and for instilling in me the centrality of faith in all that we do. I love you both so much, and I do not say it often enough! iv Abstract Advanced paternal age (APA) is related to various genetic conditions, behavioral disorders, and adverse pregnancy outcomes. Since the publication of ACMG’s practice guidelines on APA in 2008, much has been learned about the causes of paternal age effect (PAE) mutations and their clinical implications. However, no guidelines exist to refer these high-risk pregnancies to prenatal genetics care, nor are effective screening techniques presently available. As such, many patients are not fully-informed about the risks to their pregnancies due to possible APA effects, and neither are are the men who have fathered these pregnancies. Our findings support that limited APA principles are being disseminated into the general population. Additionally, prenatal patients of advanced maternal age (AMA) and their partners favor the fathers of pregnancies as important decision makers, second only to the mothers. Based on current knowledge of APA risks and molecular mechanisms, as well as our study findings, we support a collaborative effort to address the shortcomings of current prenatal genetic counseling procedure in its discussions of APA. The approach to rectify this discrepancy in prenatal genetic counseling should include a revisit of the 2008 ACMG guidelines concerning APA as well as research efforts directed toward the future goal of providing inclusive genetic counseling for men of APA and the pregnancies they father. Keywords: advanced paternal age, paternal age effect, advanced maternal age, decision making, prenatal genetic counseling v Table of Contents Dedication .......................................................................................................................... iii Acknowledgements ............................................................................................................ iv Abstract ................................................................................................................................v List of Figures ................................................................................................................... vii List of Abbreviations ....................................................................................................... viii Chapter 1: Background ........................................................................................................1 Chapter 2: The Paternal Age Effect: A Preliminary Study of Current Challenges for Prenatal Genetics Care ..............................................................................................19 2.1 Abstract ..............................................................................................................19 2.2 Introduction ........................................................................................................20 2.3 Materials and Methods .......................................................................................24 2.4 Results ................................................................................................................27 2.5 Discussion ..........................................................................................................36 2.6 Conclusions ........................................................................................................41 Chapter 3: Conclusions ......................................................................................................43 References ..........................................................................................................................44 Appendix A – Participant Materials ..................................................................................51 vi List of Figures Figure 2.1 Respondents’ knowledge regarding Down syndrome risk factors ...................29 Figure 2.2 Participants’ favor towards each representative as the decision-maker for genetic testing during pregnancy ............................................................................30 Figure 2.3 Distribution of participants’ responses to preferring maternal decision making for genetic testing versus paternal decision making (a) and preferring maternal decision making versus genetic counselor decision making (b) .............................32 Figure 2.4 Participant priority rankings for the right to make genetic testing decisions in the event that a patient and her partner do not agree on an option together ...........33 Figure 2.5 Respondents’ favorability toward prenatal or screening for conditions associated with APA ...............................................................................................34 vii List of Abbreviations ACMG............................................. American College of Medical Genetics and Genomics ACOG ........................................... American Congress of Obstetricians and Gynecologists AMA .............................................................................................. Advanced Maternal Age APA..................................................................................................Advanced Paternal Age CF .................................................................................................................. Cystic Fibrosis CVS ............................................................................................ Chorionic Villus Sampling EI .............................................................................................................. Early Intervention GWAS ............................................................................ Genome-wide Association Studies NIPS ................................................................................... Noninvasive Prenatal Screening OI ................................................................................................... Osteogenesis Imperfecta PAE .............................................................................................. (The) Paternal Age Effect RAS ..........................................................................................................(from rat sarcoma) RTK.............................................................................................. Receptor Tyrosine Kinase SNP .................................................................................. Single Nucleotide Polymorphism viii Chapter 1: Background A 2013 study conducted in Taiwan documented the clinical care for a family who was referred to prenatal genetic counseling due to maternal age and because of a previous child diagnosed with osteogenesis imperfecta (OI) (Chen et al., 2013). Following her diagnosis, a frameshift mutation was identified in the daughter, an insertion in the fifty- second exon of COL1A1. The expectant parents were ages thirty-seven years (patient) and forty-four years (partner). The curious aspect
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