Presented Abstracts from the Thirty Second Annual Education Conference of the National Society of Genetic Counselors (Anaheim, CA, October 2013)

Abstract

Noninvasive prenatal testing (NIPT) is a new technology that could dramatically increase the prenatal detection rate of Down syndrome because it lacks the risk of miscarriage inherent to invasive techniques. However, there is significant concern from the disability community and the public that it could lead to more negative attitudes toward the condition and less support for affected individuals. The goal of this study was to assess the impact NIPT may have on attitudes toward prenatal testing, Down syndrome, and parents who have a child with Down syndrome. We recruited adults through Amazon Mechanical Turk (n =1,789) to participate in an Internet-based experiment. Participants were randomly assigned either to read a hypothetical news article about NIPT, a hypothetical news article about amniocentesis, or to be part of a no article control group. The two articles were designed to be as similar as possible with the exception of the descriptions of the test characteristics. Participants then answered questions about their testing intentions and attitudes, which were analyzed using a combination of factor analysis and linear regression. Participants who read the mock news article about NIPT were much more interested in the personal use of prenatal testing than those who read the amnio-centesis article (Mean rating=4.89 vs. 2.79 on a 6 point scale, p <0.001). They also agreed more strongly that pregnant women in general should choose to test (Mean rating=4.78 vs. 3.42 on a 6 point scale, p <0.001). However, we found no cases in which the NIPT group had significantly more negative attitudes toward Down syndrome or toward parents of children with Down syndrome. These results support the conclusion that NIPT will lead to an increase in prenatal testing, but provided no evidence that NIPT will lead to more negative attitudes toward Down syndrome or parents of children with Down syndrome. Introduction: Intermediate alleles (IAs) for Huntington disease (HD) have between 27 and 35 CAG repeats. While they do not confer the HD phenotype, they are prone to paternal germline CAG repeat instability. Consequently, IAs may expand into the HD range (>36 CAG) upon transmission to the next generation producing a new mutation. Quantified risk estimates for IA repeat instability are extremely limited but urgently needed to inform genetic counseling. Methods: Using small-pool PCR of sperm DNA from Caucasian males, we examined the frequency and magnitude of CAG repeat instability across the entire range of intermediate CAG sizes. The CAG-size specific risk estimates are based on the largest sample size of IAs ever examined, including 30 IAs and 18,198 sperm. Results: Our findings demonstrate a significant risk of new mutations. While all intermediate CAG sizes demonstrated repeat expansion into the HD range, alleles with 34 and 35 CAG repeats were associated with the highest risk (2.4 % and 21.0 %, respectively). Of expansions that crossed the disease threshold, 92.6 % were within the reduced pene-trance CAG size range (36-39 CAG), compared to 7.4 % in the full penetrance range (>40 CAG). IAs with >33 CAG repeats showed a dramatic increase in the frequency of instability and a switch towards a preponderance of repeat expansions over contractions. This suggests that there may be threshold CAG length for expansion in HD around 33 repeats. Conclusion: This data provides novel insights into the origins of new mutations for HD and has significant implications for clinical practice. The paternal germline CAG-size specific risk estimates for IA repeat instability increase the accuracy of clinical risk assessment for new mutations and provides data to inform individuals reproductive decision-making.