The impact of cohort relationships on BIPOC genetic counseling students: Results from a longitudinal qualitative study.

The transition to graduate school is marked by stress, with academic demands and interpersonal interactions being primary concerns for genetic counseling students. For Black, Indigenous, and People of Color (BIPOC) graduate students, additional stressors caused by the "minority tax" and microaggressions impact their sense of belonging and inclusion. This prospective longitudinal study employed a constructivist grounded theory approach to investigate the experiences of first-year BIPOC genetic counseling students as they transitioned into the first year of their graduate training. We conducted semi-structured interviews with 26 first-year genetic counseling students at three key time points during their first year and analyzed them using reflexive thematic analysis. Here, we report themes related to stressors when transitioning into the genetic counseling training environment, the role of relationships as a source of support in navigating these challenges, and the impact of cohort dynamics on the training experience. Stressors included managing academic rigor and time demands, navigating microaggressions, reactions to discussions about diversity, equity, inclusion, and justice (DEIJ), and managing mental health. Peer relationships emerge as pivotal source of support, but challenging dynamics within the cohort negatively impacted participants, highlighting the importance of fostering an inclusive training environment. Since programs have less control over the composition of each cohort with the advent of the Match system in 2018, we recommend the use of community-building and debriefing activities to strengthen healthy relationships and address problematic dynamics. We recommend that training programs be proactive in creating mentoring relationships between faculty and students rather than waiting until students ask for help. Ultimately, we advocate for a holistic approach to genetic counseling training that maintains academic rigor but also prioritizes the creation of supportive, inclusive, and culturally sensitive learning environments for all students.

Exploring the impact of microaggressions on the genetic counseling student-supervisor relationship: A qualitative study.

Genetic counseling students with minoritized identities have reported experiencing microaggressions throughout graduate training, including from fieldwork supervisors. However, the impacts of these fieldwork experiences have not been thoroughly investigated. As supervision is known to be integral to genetic counseling students' skill development and success, the purpose of this qualitative study was to explore the impact of microaggressions on student training, with a specific focus on the supervisory working alliance. To achieve this goal, we conducted 11 interviews with recent genetic counseling graduates (2019-2021) who reported experiencing at least one microaggression from a fieldwork supervisor during graduate school training. Purposive sampling was used to prioritize interviewees who identified as underrepresented in the field due to race, ethnicity, gender identity, sexual orientation, and/or disability status. All interviewees were initially recruited as part of a larger mixed-methods study investigating the frequency and types of microaggressions genetic counseling students experience from fieldwork supervisors. Interview questions explored the time period before a microaggression event, during the event, and after. Qualitative thematic analysis resulted in four themes, three of which are presented in this paper: (1) Impact of microaggressions, (2) Barriers to reporting microaggressions, and (3) Experience reporting microaggressions. Microaggressions from supervisors were shown to impair the psychological well-being of participants and hinder learning opportunities. These experiences led participants to question their choice of profession and avoid time in clinic, ultimately constraining the development of strong supervisory working alliances. Some participants did not report microaggressions due to fear of negative repercussions, and those who did described defensive responses which harmed students' relationships with program leadership. This study reveals opportunities for supervisors to improve student training conditions by centering students' feelings and experiences, increasing open and honest communication, and extending psychosocial tools to supervision. Additionally, graduate programs are encouraged to establish structured reporting protocols for students and evaluate current shortcomings in equity and inclusion initiatives.

BIPOC students' paths to genetic counseling: Results from a longitudinal qualitative study.

Despite diversity initiatives, the genetic counseling profession continues to exhibit limited racial and ethnic diversity, with relatively stagnant representation of Black, Indigenous, and People of Color (BIPOC) individuals. Prior research has found that BIPOC high school and college students are less likely to be aware of genetic counseling and learn about it later than their white peers. Financial barriers and familial discouragement based on a preference for medical school may disproportionately impact BIPOC applicants. Here, we report the first set of results from a longitudinal constructivist grounded theory study exploring the training experiences of BIPOC genetic counseling students. Through reflexive thematic analysis of semi-structured interviews conducted with 26 first-year BIPOC genetic counseling students, we identified five themes pertaining to participants' paths to enrolling in a genetic counseling program: (1) Deciding to pursue genetic counseling, (2) Family's reaction to genetic counseling, (3) Deciding where to submit applications, (4) Barriers during admissions, and (5) Ranking programs. Participants discovered genetic counseling later in their academic journey, often necessitating gap years to complete admissions requirements. Limited guidance from advisors was commonly cited as a barrier by first-generation college students. Family support seems to be a key factor in participants' successful pursuit of genetic counseling, but participants described challenges explaining the career, particularly to parents who did not speak English. In addition, some participants encountered resistance about changing prior plans to go to medical school. Finally, while participants prioritized cost and location in their initial decision about where to submit applications, their ranking of programs was heavily influenced by experiences during interviews, where they favored conversational interviews and evaluated if they would "fit in" at the program. These findings underscore the need for proactive measures, such as early exposure initiatives, mentorship programs, and resources to facilitate family support, to promote diversity in genetic counseling.

Exploring the occurrence of microaggressions in the genetic counseling student-supervisor relationship: A mixed-methods study.

While research has shown that genetic counseling students with minoritized racial or ethnic identities face microaggressions throughout graduate training, quantitative data regarding the frequency of these experiences have not been reported. The purpose of this mixed-methods study was to investigate the frequency and types of microaggressions experienced by graduates of accredited genetic counseling programs in the United States during fieldwork rotations. A quantitative survey was administered to assess how frequently 14 different types of microaggressions occurred in interactions with supervisors. Survey responses were analyzed using situation-based coding (the number of different types of microaggressions experienced) and frequency-based coding (the sum of participants' weighted Likert answers). Select survey respondents with minoritized identities were interviewed to better contextualize and categorize microaggression experiences. Analysis of 87 survey responses revealed that participants with minoritized racial and ethnic identities experience significantly more types of microaggressions (t(61) = 2.77; p = 0.007) at a significantly higher frequency (t(55) = 2.67; p = 0.010) than their white counterparts. Participants who identified as part of the disability community were also found to experience significantly more types of microaggressions (t(10) = 3.25; p = 0.009) at a significantly higher frequency (t(9) = 2.32; p = 0.045) than those who did not. Qualitative analysis of 11 interviews revealed that microaggressions from supervisors included offensive and inappropriate comments, unequal treatment, cultural intolerance, and disparaging feedback. Overall, our data present evidence that students with minoritized racial and ethnic identities and students with disabilities are subjected to a variety of inequitable, exclusionary, and harmful interactions. As a result, we recommend that all supervisors receive training about recognizing and preventing microaggressions to ensure that students are provided with an equitable and inclusive training experience, regardless of identity.

A qualitative study of LGBTQIA+ genetic counselors' experiences while applying to graduate school.

Research has shown that lesbian, gay, bisexual, transgender, queer, intersex, asexual and other sexual and gender minority (LGBTQIA+) healthcare students experience discrimination during admissions and training. While several studies have examined the experiences of racial and ethnic minorities within the genetic counseling field, the admissions experiences of LGBTQIA+ individuals have not been explored. Through semi-structured interviews, this qualitative study investigated the experiences of ten LGBTQIA+ genetic counselors and genetic counseling students during graduate school admissions. Interview questions focused on participants' perceptions of the genetic counseling field prior to applying, important factors in choosing and ranking programs, decisions surrounding disclosure of LGBTQIA+ identities, interview experiences related to their identities, and the impacts, if any, of their identities on their overall admissions journey. Transcripts were coded and analyzed utilizing a constructivist grounded theory approach, resulting in the emergence of themes regarding factors that influenced participants' decisions to disclose their identity and how their LGBTQIA+ identity factored into their selection of a training program. This study adds new perspectives to the conversations around diversity, equity, and inclusion within the genetic counseling field. Further, it provides genetic counselors and genetic counseling programs insight into inclusive admissions processes and suggests ways to improve inclusivity in graduate admissions.

A qualitative study exploring LGBTQ genetic counseling students' relationships with peers and faculty in graduate school.

Lesbian, gay, bisexual, transgender, queer/questioning, and other sexual and gender minority (LGBTQ) students in healthcare professional programs face discrimination in their training, leading them to hide their identities and hindering their ability to form as meaningful connections with their classmates and faculty as non-LGBTQ students. To date, no studies have been published characterizing the LGBTQ student experience in genetic counseling programs. However, other historically oppressed groups such as Black, Indigenous, and people of color (BIPOC) genetic counseling students report feelings of isolation and negative impacts on mental health due to their racial or ethnic identity. This study explored how LGBTQ identity impacted relationships between genetic counseling students and their classmates and faculty in graduate school. In this qualitative study using constructivist grounded theory, 13 LGBTQ students and recent graduates of Canadian and American accredited genetic counseling programs were interviewed via videoconferencing. Participants reported determinants in self-disclosing their LGBTQ identity to their classmates and faculty and described ways in which their LGBTQ identity impacted relationships with individuals in their training programs. In particular, many described an overall heteronormative training environment, a hesitation to disclose their identity to faculty due to the professional nature of the relationship, and a sense of isolation. Participants also described the ways in which intersecting minoritized identities impacted their experiences as an LGBTQ student. This research contributes to the minimal literature about LGBTQ genetic counseling student experiences and has implications for addressing cisheteronormative curricula and attitudes in genetic counseling programs.

The Role of Genetic Testing in Pulmonary Fibrosis: A Perspective From the Pulmonary Fibrosis Foundation Genetic Testing Work Group.

Patients with familial pulmonary fibrosis represent a subset of patients with pulmonary fibrosis in whom inherited gene variation predisposes them to disease development. In the appropriate setting, genetic testing allows for personalized assessment of disease, recognition of clinically relevant extrapulmonary manifestations, and assessing susceptibility in unaffected relatives. However currently, the use of genetic testing is inconsistent, partly because of the lack of guidance regarding high-yield scenarios in which the results of genetic testing can inform clinical decision-making. To address this, the Pulmonary Fibrosis Foundation commissioned a genetic testing work group comprising pulmonologists, geneticists, and genetic counselors from the United States to provide guidance on genetic testing in patients with pulmonary fibrosis. This CHEST special feature presents a concise review of these proceedings and reviews pulmonary fibrosis susceptibility, clinically available genetic testing methods, and clinical scenarios in which genetic testing should be considered.

Examining clinical training through a bicultural lens: Experiences of genetic counseling students who identify with a racial or ethnic minority group.

Biculturals are individuals who have had significant exposure to more than one culture and who possess more than one cultural frame of reference. In the United States, this term has been used to describe both immigrants and members of racial or ethnic minority groups who live within the majority white culture. Biculturals develop a distinct repertoire of social and cognitive skills and have been shown to engage in a process of cultural frame switching in response to salient cultural cues. Through a conceptual lens offered by current research on biculturalism, this article examines transcripts of focus groups we collected for a study on the clinical training experiences of genetic counseling students who identify with a racial or ethnic minority group. We conducted a constructivist grounded theory study, collecting data via 13 videoconference focus groups with 32 recent graduates of genetic counseling training programs who identify with a racial or ethnic minority group. We focus here on two of the thematic categories identified in that study related to participants' experiences interacting with patients during supervised clinical rotations. We find three ways in which being bicultural influenced these genetic counselors' patient interactions. First, participants described interactions with both culturally concordant and culturally discordant patients that highlighted the salience of their racial, ethnic, or cultural identity in these encounters. Second, they reported sensitivity to social nuances between and within cultures, reflecting the findings of prior research about heightened cultural awareness in biculturals. Third, they described switching cultural frames in response to their patients' identities which, at times, created conflict between their professional and culturally concordant frameworks. The results of this study suggest that the influence of a student's racial, ethnic, or cultural identity on interactions with patients should be discussed within the supervisory relationship, and that being bicultural confers advantages in learning to provide culturally responsive care.

Transgender patients' perspectives on their cancer genetic counseling experiences.

Transgender (trans) individuals face many forms of discrimination in accessing health care, including lack of provider knowledge and denial of services. Barriers specific to the cancer setting include limited availability of information concerning cancer management and its potential impact on gender affirmation therapies and minimal training for providers regarding inclusive practices for the trans population. The limited research about the experiences of cancer genetic counseling for trans patients has investigated exclusively the perspective of the provider, not the patient. This constructivist grounded theory study sought to fill this gap in the literature by interviewing trans individuals who had undergone cancer genetic counseling. Participants were recruited through social media platforms, LGBTQ+ advocacy and cancer support groups, and the National Society of Genetic Counselors' list serv. Six semi-structured interviews were conducted with participants focusing on their expectations and goals prior to the genetic counseling session, concerns during the session, and reflections on inclusive practices. Transcripts were coded and analyzed using a constant comparative approach and five themes emerged: (a) Anxiety for the consult, (b) Disruptions of familial relationships and emotional support systems, (c) Use of inclusive language during session, (d) Impact on gender affirmation journey, and (e) Lack of appropriate cancer risk information for trans patients. The results from this pilot study suggest that trans patients experience anticipatory anxiety before the genetic counseling appointment, particularly about the potential of a physical examination. They may be more likely to experience disrupted family relationships that impact access to family history information and support. Genetic counselors should utilize inclusive language both when referring to the patient and when discussing cancer risk. Finally, additional research is needed to provide more accurate cancer risk predictions for trans individuals.

Variants in STXBP3 are Associated with Very Early Onset Inflammatory Bowel Disease, Bilateral Sensorineural Hearing Loss and Immune Dysregulation.

BACKGROUND AND AIMS: Very early onset inflammatory bowel disease [VEOIBD] is characterized by intestinal inflammation affecting infants and children less than 6 years of age. To date, over 60 monogenic aetiologies of VEOIBD have been identified, many characterized by highly penetrant recessive or dominant variants in underlying immune and/or epithelial pathways. We sought to identify the genetic cause of VEOIBD in a subset of patients with a unique clinical presentation. METHODS: Whole exome sequencing was performed on five families with ten patients who presented with a similar constellation of symptoms including medically refractory infantile-onset IBD, bilateral sensorineural hearing loss and, in the majority, recurrent infections. Genetic aetiologies of VEOIBD were assessed and Sanger sequencing was performed to confirm novel genetic findings. Western analysis on peripheral blood mononuclear cells and functional studies with epithelial cell lines were employed. RESULTS: In each of the ten patients, we identified damaging heterozygous or biallelic variants in the Syntaxin-Binding Protein 3 gene [STXBP3], a protein known to regulate intracellular vesicular trafficking in the syntaxin-binding protein family of molecules, but not associated to date with either VEOIBD or sensorineural hearing loss. These mutations interfere with either intron splicing or protein stability and lead to reduced STXBP3 protein expression. Knock-down of STXBP3 in CaCo2 cells resulted in defects in cell polarity. CONCLUSION: Overall, we describe a novel genetic syndrome and identify a critical role for STXBP3 in VEOIBD, sensorineural hearing loss and immune dysregulation.

Supporting a sense of inclusion and belonging for genetic counseling students who identify as racial or ethnic minorities.

Racial and ethnic minority graduate students in a variety of academic and professional disciplines have been reported to experience microaggressions and feelings of isolation during the course of their training. The purpose of this constructivist grounded theory study was to characterize the training experiences of genetic counseling students who identify as racial or ethnic minorities. The goal of enhancing racial and ethnic diversity has been discussed for decades within the genetic counseling profession, but the actual training experience of underrepresented minorities has yet to be fully explored. We conducted 13 videoconference focus groups with 32 recent graduates of genetic counseling training programs who identify as racial or ethnic minorities. This paper presents results from three of the thematic categories identified in that larger study: Participants' interactions with classmates, Sense of belonging in the GC profession, and Available or desired supports. Participants reported experiencing negative interactions within their training program, during supervised clinical rotations, and at professional events; negative interactions included comments suggesting they did not belong in the United States, being confused with another non-white classmate, and intrusive questions or assumptions about their family, culture, or religion that were not similarly directed at white classmates. Trainees who were Muslim or Black/African American reported feeling particularly isolated by these incidents. Participants reported that they sought support from a variety of sources following negative experiences. Non-minority program faculty were perceived as able to offer listening or action but not understanding or guidance, which were perceived as more likely to be available from individuals who identify as racial or ethnic minorities. Results of this exploratory study suggest the need for training programs to ensure that appropriate supports are available to minority students, including diverse faculty and staff and non-program resources.

Psychological impact of genetic and clinical screening for pulmonary fibrosis on asymptomatic first-degree relatives of affected individuals.

Screening for pulmonary fibrosis may help to identify early stages of the disease. We assessed the psychological impact of screening undiagnosed first-degree relatives of patients with pulmonary fibrosis by administering two validated measures after participants received their results: the Decisional Regret Scale and the Feelings About genomiC Testing Results Questionnaire. More than 90% of relatives reported either no or mild decisional regret. Increased measures of decisional regret and negative feelings were present in those found to have a low diffusion capacity of carbon monoxide or interstitial lung abnormalities. Results of telomere length and genetic testing did not significantly impact regret.

ALX1-related frontonasal dysplasia results from defective neural crest cell development and migration.

A pedigree of subjects presented with frontonasal dysplasia (FND). Genome sequencing and analysis identified a p.L165F missense variant in the homeodomain of the transcription factor ALX1 which was imputed to be pathogenic. Induced pluripotent stem cells (iPSC) were derived from the subjects and differentiated to neural crest cells (NCC). NCC derived from ALX1L165F/L165F iPSC were more sensitive to apoptosis, showed an elevated expression of several neural crest progenitor state markers, and exhibited impaired migration compared to wild-type controls. NCC migration was evaluated in vivo using lineage tracing in a zebrafish model, which revealed defective migration of the anterior NCC stream that contributes to the median portion of the anterior neurocranium, phenocopying the clinical presentation. Analysis of human NCC culture media revealed a change in the level of bone morphogenic proteins (BMP), with a low level of BMP2 and a high level of BMP9. Soluble BMP2 and BMP9 antagonist treatments were able to rescue the defective migration phenotype. Taken together, these results demonstrate a mechanistic requirement of ALX1 in NCC development and migration.

De novo mutations in TOMM70, a receptor of the mitochondrial import translocase, cause neurological impairment.

The translocase of outer mitochondrial membrane (TOMM) complex is the entry gate for virtually all mitochondrial proteins and is essential to build the mitochondrial proteome. TOMM70 is a receptor that assists mainly in mitochondrial protein import. Here, we report two individuals with de novo variants in the C-terminal region of TOMM70. While both individuals exhibited shared symptoms including hypotonia, hyper-reflexia, ataxia, dystonia and significant white matter abnormalities, there were differences between the two individuals, most prominently the age of symptom onset. Both individuals were undiagnosed despite extensive genetics workups. Individual 1 was found to have a p.Thr607Ile variant while Individual 2 was found to have a p.Ile554Phe variant in TOMM70. To functionally assess both TOMM70 variants, we replaced the Drosophila Tom70 coding region with a Kozak-mini-GAL4 transgene using CRISPR-Cas9. Homozygous mutant animals die as pupae, but lethality is rescued by the mini-GAL4-driven expression of human UAS-TOMM70 cDNA. Both modeled variants lead to significantly less rescue indicating that they are loss-of-function alleles. Similarly, RNAi-mediated knockdown of Tom70 in the developing eye causes roughening and synaptic transmission defect, common findings in neurodegenerative and mitochondrial disorders. These phenotypes were rescued by the reference, but not the variants, of TOMM70. Altogether, our data indicate that de novo loss-of-function variants in TOMM70 result in variable white matter disease and neurological phenotypes in affected individuals.

Conscripted curriculum: The experiences of minority genetic counseling students.

While the lack of racial and ethnic diversity in the genetic counseling profession has been discussed for decades, little attention has been paid to the training experiences of under-represented minorities. Under-represented minority graduate students in other disciplines have been reported to experience microaggressions and feelings of isolation during training, and they are often informally enlisted to educate classmates about issues related to race. In 2019, sociologist Lauren Olsen coined the term conscripted curriculum to describe the utilization of minority medical students to elucidate issues of race or ethnicity for their classmates. The conscripted curriculum arises when these topics are taught in a small-group discussion format that relies on students sharing their individual experiences to educate their classmates. In classrooms with limited diversity, the expectation to contribute falls disproportionately on students from non-majority groups. In this qualitative study, we conducted videoconference focus groups with 32 recent graduates of genetic counseling training programs who identified as racial or ethnic minorities. We present the results of two thematic categories that emerged from that study: the participants' perspectives on the cultural competency curriculum in their training programs and the participants' feelings of being pressed into service as spokespeople for their cultural groups. Participants described the cultural competency training as occurring primarily in a small-group discussion format in which students were expected to share their personal experiences. During these discussions, minority students, especially those in less-diverse class cohorts, felt obliged to contribute their perspectives in order to educate non-minority classmates about issues of race and ethnicity, leading to feelings of frustration and exhaustion. The results reflect a conscripted curriculum as described by Olsen (2019). Journal of Health and Social Behavior, 60(1), 55-68, in which minority students bear the burden of educating their classmates about the social basis of race. Genetic counseling training programs should critically examine their cultural competency curriculum to create a more equitable training environment.

Interstitial Lung Disease in Relatives of Patients with Pulmonary Fibrosis.

Rationale: Although relatives of patients with familial pulmonary fibrosis (FPF) are at an increased risk for interstitial lung disease (ILD), the risk among relatives of sporadic idiopathic pulmonary fibrosis (IPF) is not known.Objectives: To identify the prevalence of interstitial lung abnormalities (ILA) and ILD among relatives of patients with FPF and sporadic IPF.Methods: Undiagnosed first-degree relatives of patients with pulmonary fibrosis (PF) consented to participate in a screening study that included the completion of questionnaires, pulmonary function testing, chest computed tomography, a blood sample collection for immunophenotyping, telomere length assessments, and genetic testing.Measurements and Main Results: Of the 105 relatives in the study, 33 (31%) had ILA, whereas 72 (69%) were either indeterminate or had no ILA. Of the 33 relatives with ILA, 19 (58%) had further evidence for ILD (defined by the combination of imaging findings and pulmonary function testing decrements). There was no evidence in multivariable analyses that the prevalence of either ILA or ILD differed between the 46 relatives with FPF and the 59 relatives with sporadic IPF. Relatives with decrements in either total lung or diffusion capacity had a greater than 9-fold increase in their odds of having ILA (odds ratio, 9.6; 95% confidence interval, 3.1-29.8; P < 0.001).Conclusions: An undiagnosed form of ILD may be present in greater than 1 in 6 older first-degree relatives of patients with PF. First-degree relatives of patients with both familial and sporadic IPF appear to be at similar risk. Our findings suggest that screening for PF in relatives might be warranted.

Homozygous TRPV4 mutation causes congenital distal spinal muscular atrophy and arthrogryposis.

OBJECTIVE: To identify the genetic cause of disease in a form of congenital spinal muscular atrophy and arthrogryposis (CSMAA). METHODS: A 2-year-old boy was diagnosed with arthrogryposis multiplex congenita, severe skeletal abnormalities, torticollis, vocal cord paralysis, and diminished lower limb movement. Whole-exome sequencing (WES) was performed on the proband and family members. In silico modeling of protein structure and heterologous protein expression and cytotoxicity assays were performed to validate pathogenicity of the identified variant. RESULTS: WES revealed a homozygous mutation in the TRPV4 gene (c.281C>T; p.S94L). The identification of a recessive mutation in TRPV4 extends the spectrum of mutations in recessive forms of the TRPV4-associated disease. p.S94L and other previously identified TRPV4 variants in different protein domains were compared in structural modeling and functional studies. In silico structural modeling suggests that the p.S94L mutation is in the disordered N-terminal region proximal to important regulatory binding sites for phosphoinositides and for PACSIN3, which could lead to alterations in trafficking and/or channel sensitivity. Functional studies by Western blot and immunohistochemical analysis show that p.S94L increased TRPV4 activity-based cytotoxicity and resultant decreased TRPV4 expression levels, therefore involves a gain-of-function mechanism. CONCLUSIONS: This study identifies a novel homozygous mutation in TRPV4 as a cause of the recessive form of CSMAA.

An integrated clinical program and crowdsourcing strategy for genomic sequencing and Mendelian disease gene discovery.

Despite major progress in defining the genetic basis of Mendelian disorders, the molecular etiology of many cases remains unknown. Patients with these undiagnosed disorders often have complex presentations and require treatment by multiple health care specialists. Here, we describe an integrated clinical diagnostic and research program using whole-exome and whole-genome sequencing (WES/WGS) for Mendelian disease gene discovery. This program employs specific case ascertainment parameters, a WES/WGS computational analysis pipeline that is optimized for Mendelian disease gene discovery with variant callers tuned to specific inheritance modes, an interdisciplinary crowdsourcing strategy for genomic sequence analysis, matchmaking for additional cases, and integration of the findings regarding gene causality with the clinical management plan. The interdisciplinary gene discovery team includes clinical, computational, and experimental biomedical specialists who interact to identify the genetic etiology of the disease, and when so warranted, to devise improved or novel treatments for affected patients. This program effectively integrates the clinical and research missions of an academic medical center and affords both diagnostic and therapeutic options for patients suffering from genetic disease. It may therefore be germane to other academic medical institutions engaged in implementing genomic medicine programs.