Motivators for participation in a whole-genome sequencing study: implications for translational genomics research.

The promise of personalized medicine depends on the ability to integrate genetic sequencing information into disease risk assessment for individuals. As genomic sequencing technology enters the realm of clinical care, its scale necessitates answers to key social and behavioral research questions about the complexities of understanding, communicating, and ultimately using sequence information to improve health. Our study captured the motivations and expectations of research participants who consented to participate in a research protocol, ClinSeq, which offers to return a subset of the data generated through high-throughput sequencing. We present findings from an exploratory study of 322 participants, most of whom identified themselves as white, non-Hispanic, and coming from higher socio-economic groups. Participants aged 45-65 years answered open-ended questions about the reasons they consented to ClinSeq and about what they anticipated would come of genomic sequencing. Two main reasons for participating were as follows: a conviction to altruism in promoting research, and a desire to learn more about genetic factors that contribute to one's own health risk. Overall, participants expected genomic research to help improve understanding of disease causes and treatments. Our findings offer a first glimpse into the motivations and expectations of individuals seeking their own genomic information, and provide initial insights into the value these early adopters of technology place on information generated by high-throughput sequencing studies.

MRI features of 4 female patients with pyruvate dehydrogenase E1 alpha deficiency.

Pyruvate dehydrogenase complex is a key intramitochondrial multienzyme complex required for the conversion of pyruvate to acetyl-CoA. Most patients with pyruvate dehydrogenase deficiency have a defect in the E1 alpha subunit, associated with mutations in the PDHA1 gene. In this report, we submit detailed magnetic resonance images in 4 affected female patients with PDHA1 mutations who had with severe cortical atrophy, dilated ventricles, and an incomplete corpus callosum. In one of these patients, the magnetic resonance imaging pattern prompted molecular diagnostic testing when enzymatic testing was normal. We underscore that this constellation of features, which may be misdiagnosed as periventricular leukomalacia, illustrates a pattern highly suggestive of a deficiency of pyruvate dehydrogenase E1 alpha in female patients and should trigger appropriate diagnostic investigations.

Focal central white matter lesions in Alexander disease.

Alexander disease is a neurodegenerative disorder of the central white matter caused by dominant mutations in GFAP, the gene encoding glial fibrillary acidic protein. Magnetic resonance imaging pattern recognition studies have established characteristic radiologic phenotypes for this disorder. In some cases, however, genetically confirmed cases do not express these features, and several reports have identified "atypical" radiologic findings in Alexander disease patients. Here, the authors report 3 genetically confirmed Alexander disease cases with focal central white matter lesions that, upon longitudinal clinical and radiologic evaluation, appear to reflect an atypical Alexander disease magnetic resonance imaging phenotype and not another pathophysiologic process such as encephalitis, infarction, or neoplasm.

Testing the effects of educational strategies on comprehension of a genomic concept using virtual reality technology.

OBJECTIVE: Applying genetic susceptibility information to improve health will likely require educating patients about abstract concepts, for which there is little existing research. This experimental study examined the effect of learning mode on comprehension of a genomic concept. METHODS: 156 individuals aged 18-40 without specialized knowledge were randomly assigned to either a virtual reality active learning or didactic learning condition. The outcome was comprehension (recall, transfer, mental models). RESULTS: Change in recall was greater for didactic learning than for active learning (p<0.001). Mean transfer and change in mental models were also higher for didactic learning (p<0.0001 and p<0.05, respectively). Believability was higher for didactic learning (p<0.05), while ratings for motivation (p<0.05), interest (p<0.0001), and enjoyment (p<0.0001) were higher for active learning, but these variables did not mediate the association between learning mode and comprehension. CONCLUSION: These results show that learning mode affects comprehension, but additional research is needed regarding how and in what contexts different approaches are best for educating patients about abstract concepts. PRACTICE IMPLICATIONS: Didactic, interpersonal health education approaches may be more effective than interactive games in educating patients about abstract, unfamiliar concepts. These findings indicate the importance of traditional health education approaches in emerging areas like genomics.

The art of coping with a craniofacial difference: helping others through "Positive Exposure".

Finding ways to cope with social stigmatization is an important aspect of achieving adaptation for people living with visible genetic differences. This study describes the way individuals with craniofacial differences use an innovative photography and video experience with Positive Exposure (PE), a non-profit organization based in New York City, as a way to cope with their conditions. Thirty-five individuals between 12 and 61 years of age participated in this study. We administered surveys comprised of open-ended qualitative questions and quantitative measures designed to assess self-esteem, perceived stigma, and hopefulness. Data for this analysis was generated from the written questionnaires and interview transcripts. Most participants reported high levels of self-esteem and hopefulness, suggesting that they were relatively well adapted to their condition. Almost all participants described experiences of stigmatization throughout their lives. However, participants demonstrated their ability to implement a variety of coping strategies to manage stigma. "Helping others" emerged as a prominent strategy among participants, aiding in the often lifelong process of adapting to their genetic difference. PE was described as an avenue through which participants could reach out to individuals and society at large, helping them adapt further to their condition. "Helping others" may also benefit individuals with craniofacial differences who do not consider themselves to be well adapted to their condition. Health care providers can collaborate with PE, advocacy groups and other community or support groups to identify additional ways individuals with craniofacial differences can help themselves by reaching out to others.