Direct to consumer (DTC) personal genetic testing (PGT) is a popular choice for individuals in the United States who are interested in learning more about their genetic health risks without formally seeing a medical professional. The company 23andMe offers FDA-approved genetic risk tests for conditions including late-onset Alzheimer’s Disease (AD), Parkinson Disease, Celiac Disease, and the BRCA1/2 mutations. Although this company’s genetic risk testing results are accompanied by a generic information sheet regarding what each individual’s result means for each condition, formal genetic counseling is not included in the service. However, when a condition such as late-onset AD has both known genetic and behavioral risk factors, counseling becomes essential in preventing or delaying disease onset. Following a Mediterranean-style diet, regularly exercising, and regularly participating in cognitive activities (e.g. reading the newspaper or playing a musical instrument) are each thought to be protective against developing late-onset AD. Previous studies have shown that customers do not usually make significant lifestyle modifications after completing DTC PGT, though the majority of this literature may not be relevant to late-onset AD as it included customers of DTC PGT companies that no longer exist today and the genetic risk test for late-onset AD at that time was not yet approved by the Food and Drug Administration. The proposed study is an interventional study that will compare DTC PGT customer exercise, diet, and cognitive activity habits before and after a personalized genetics counseling session. Exercise will be measured using the Godin-Leisure Time Exercise Questionnaire. Diet will be evaluated by a validated food frequency questionnaire evaluating daily servings of fruits, vegetables, and unprocessed nuts. Cognitive activity at the time of survey will be evaluated by a questionnaire asking for the frequency of various cognitive activities, such as reading newspapers, reading books, artistic activities, and social activities.

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ABSTRACT Huntington Disease (HD) is a neurodegenerative disorder that is inherited in an autosomal dominant manner, and for which testing is available. The aim of this retrospective file-based study was to analyse the numbers and demographics of individuals who had diagnostic, predictive or prenatal genetic counselling and/or testing for HD between January 1998 and December 2006 through the Division of Human Genetics, National Health Laboratory Service and University of the Witwatersrand, Johannesburg. Files for 287 individuals who had genetic counselling and/or testing for HD were included in this study, with 77% being diagnostic cases, 20% predictive and 3% prenatal. When the results obtained in this study were compared to a study by Kromberg et al. (1999) done previously in the same Division, it was found that there has been an increase in the number of diagnostic and predictive tests done per year during this study, with diagnostic tests making up a greater percentage of the total number of tests performed. One of the objectives of this study was to characterise the individuals who requested HD testing and to compare the characteristics of those in the diagnostic testing group to those in the predictive testing group. The median age of the individuals in the predictive testing group was 30 years, which was significantly different from the median age of 49 years for individuals in the diagnostic testing group (p<0.001). It was found that there were significantly more women than men requesting predictive testing (p=0.02), while the number of males and females in the diagnostic testing group was similar (p=1.00). There was also a greater percentage of employed (76.4%) versus unemployed (23.6%) individuals in the predictive testing group, while the percentages of employed and unemployed individuals in the diagnostic testing group were similar (45.5% and 54.5% respectively). Significantly more individuals in the diagnostic testing group had children (74.5%) compared to those in the predictive testing group, where 44.6% of individuals had one or more children. There was a greater percentage of white individuals in the predictive testing group (91% white; 3.5% black) compared to the diagnostic testing group (48% white, 42% black). The completion rate of the predictive testing process was 66.7%. In the predictive testing group, 39.5% of individuals tested positive for HD, and in the diagnostic testing group 53% of individuals tested positive for HD. Nine prenatal tests were requested by five different couples, and 7 tests were performed. Three of these fetuses tested positive for HD (including a set of twins) and these two pregnancies were terminated. Overall, there seems to be a lack of awareness of and/or access to the genetic services offered for HD through the Division of Human Genetics, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, particularly among black individuals and the professionals treating them. Information generated from this study can be used to understand the individuals seeking genetic counselling and/or testing for HD better, and can direct efforts to improve awareness and access amongst groups noted to be under-represented. It also serves as a starting point for further research.

Deafness is the most common sensory deficit in humans. In the United States 1-2 in a thousand babies is born with significant deafness, well over half of which is hereditary. Providing a patient and their family with a genetic diagnosis is the ultimate form of precision health and medicine; it can provide education, impact medical testing and treatment, provide peace of mind, and someday will be the key to providing gene specific therapies. Historically, providing this diagnosis was difficult, expensive, and time consuming due to the extreme clinical and genetic heterogeneity of non-syndromic hearing loss (NSHL). Targeted genomic enrichment and massively parallel sequencing (TGE+MPS) have revolutionized the field of precision health and medicine, allowing for comprehensive genetic diagnosis of many complicated conditions, including NSHL. To take advantage of this advance in technology, the OtoSCOPE® platform was created, targeting all known deafness-causing genes and creating the first comprehensive genetic test for this condition. With the implementation of OtoSCOPE® we aspire to accomplish two aims: providing comprehensive genetic diagnosis for patients all over the world and characterizing the full spectrum of hereditary hearing loss. The goal of my thesis work has been to use OtoSCOPE® to better understand the landscape of NSHL in multiple populations and to use this knowledge to further optimize it to be the most effective and tailored diagnostic tool possible for individuals with deafness. In order to achieve these goals, we investigated a few unique populations. We first evaluated the effectiveness of diagnosis of OtoSCOPE® on two preselected cohorts of 302 Iranian and 9 Cameroonian probands with autosomal recessive NSHL (ARNSHL). We can now better define the frequent causes of NSHL in Iranians with a high degree of inbreeding, and begin to understand the spectrum of deafness in Sub-Saharan Africa that has previously been underutilized. Next we sought to determine the spectrum of hearing loss within a clinical cohort in the United States by evaluating 1119 sequentially accrued probands for whom the OtoSCOPE® panel was ordered as a diagnostic test. This analysis allowed us to determine the overall diagnostic success of OtoSCOPE® (39%), the most common genes responsible for NSHL, the overall breadth of genes that can be identified within a cohort like this (49 genes), and patient characteristics which impact the likelihood of providing a positive diagnosis. This study permitted us to recommend use of OtoSCOPE® or other TGE+MPS diagnostic tools early in the diagnostic process of a patient with NSHL. Finally, we interrogated the contribution of syndromic forms of deafness which may actually manifest as NSHL (NSHL mimics) within two deafness cohorts. We performed a retrospective chart review of 14 families with syndromic deafness seen by the Genetic-Eye-Ear Clinics to determine which methods are the most efficient and effective at providing an accurate diagnosis through the combination of collaborative clinical and molecular genetic diagnostic tools. We also performed a secondary analysis of 2384 sequentially accrued probands clinically evaluated with OtoSCOPE®, specifically evaluating the impact of panel versioning and inclusion of additional NSHL mimics. We recommend use of OtoSCOPE® as a diagnostic tool to most patients with apparent NSHL, and utilize an automatic positive feedback loop to ensure the most comprehensive and accurate diagnosis possible. All of these studies have lead to the better understanding of the genes and variants that cause NSHL and its mimics, providing a more accurate genetic diagnosis, which is prerequisite to a future of targeted genetic therapies.

This article reports on consumer interactions with and impressions of self-administered online genetic testing results through a direct-to-consumer (DTC) genetic testing service, 23 and Me. Participants in this study point out a clear need for greater education about genetic testing services, increased considerations of health literacy barriers in results communication, and point to larger marketing, advertising, and public health industry implications as they relate to DTC genetic testing. / text

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A 41-year-old woman presented with burning and erythema in her extremities triggered by warmth and activity, which was relieved by applying ice. Extensive workup was consistent with adult-onset primary erythromelalgia (EM). Several pharmacological treatments were tried including local anesthetics, capsaicin, ziconotide, and dantrolene, all providing 24-48 hours of relief followed by symptom flare. Interventional therapies, including peripheral and sympathetic ganglion blocks, also failed. Thus far, clonidine and ketamine have been the only effective agents for our patient. Genetic testing was negative for an EM-associated mutation in the SCN9A gene, encoding the Na(V)1.7 sodium channel, suggesting a mutation in an alternate gene.

Scientific developments in genetics receive great public and political attention. However, genetic tests as medical innovations need to travel from the laboratory to the individual patient in order to fulfil the goal that makes the science so attractive. A medical innovation has to pass through the institutions of diverse health care systems. This thesis compares how the structures of two very different health care systems in Europe (Germany and the UK) foster or hinder the diffusion of genetic technologies. It presents a detailed analysis of the institutional pathways involved in order to discuss whether and in which way the kind of medical innovation that genetic testing represents is accommodated. The case study used for analysing the passage of a genetic test in both countries is diagnostic testing for Maturity Onset Diabetes of the Young (MODY). This example has the idiosyncratic dimension that it had strong support by scientists and government when the UK Government prioritized genetics in health policy. However, MODY testing was chosen for this study because MODY is a ‘simple’ monogenetic test, and it is one of the few at present that are both reliable and lead to altered treatment with a better quality of life for the patient. MODY represents, according to the current state of genomic knowledge, a prime example of what genetics is likely to deliver at best over the coming decades. In brief, the comparison of the pathways MODY travelled and the degree to which it reached patients successfully shows that both systems are not optimally set up to exploit what MODY genetic testing has to offer, but that the vertical structure and centralization in the UK system fit the needs of genetic medical innovations better than the horizontal, diversified and market oriented structures dominating the German health care system.