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Michael Talkowski and colleagues analyze balanced chromosomal abnormalities in 273 individuals by whole-genome sequencing. Their findings suggest that sequence-level resolution improves prediction of clinical outcomes for balanced rearrangements and provides insight into pathogenic mechanisms such as altered gene regulation due to changes in chromosome topology. Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C , a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology.

Biallelic mutations of UBE3B have recently been shown to cause Kaufman oculocerebrofacial syndrome (also reported as blepharophimosis–ptosis–intellectual disability syndrome), an autosomal recessive condition characterized by hypotonia, developmental delay, intellectual disability, congenital anomalies, characteristic facial dysmorphic features, and low cholesterol levels. To date, six patients with either missense mutations affecting the UBE3B HECT domain or truncating mutations have been described. Here, we report on the identification of homozygous or compound heterozygous UBE3B mutations in six additional patients from five unrelated families using either targeted UBE3B sequencing in individuals with suggestive facial dysmorphic features, or exome sequencing. Our results expand the clinical and mutational spectrum of the UBE3B -related disorder in several ways. First, we have identified UBE3B mutations in individuals who previously received distinct clinical diagnoses: two sibs with Toriello–Carey syndrome as well as the patient reported to have a “new” syndrome by Buntinx and Majewski in 1990. Second, we describe the adult phenotype and clinical variability of the syndrome. Third, we report on the first instance of homozygous missense alterations outside the HECT domain of UBE3B, observed in a patient with mildly dysmorphic facial features. We conclude that UBE3B mutations cause a clinically recognizable and possibly underdiagnosed syndrome characterized by distinct craniofacial features, hypotonia, failure to thrive, eye abnormalities, other congenital malformations, low cholesterol levels, and severe intellectual disability. We review the UBE3B -associated phenotypes, including forms that can mimick Toriello–Carey syndrome, and suggest the single designation “Kaufman oculocerebrofacial syndrome”.

With decreasing inpatient rehabilitation lengths of stay, there may be a greater risk of spinal cord injury (SCI) populations being discharged into the community without the self-management skills needed to prevent secondary complications. Recent advancements in mobile health has made mobile apps a feasible method of delivering population-based, self-management interventions to address SCI-specific secondary complications. The objective of this study is to describe stakeholder perspectives on the development of a functional mobile app to facilitate self-management skills needed to prevent secondary complications following recent SCI during inpatient rehabilitation. A user-centered design approach was used that involved an evolving mobile app and the collection of prospective qualitative data. Stakeholders from three groups were enrolled in the study: individuals admitted for rehabilitation following SCI (n = 20) and informal (n = 7) and formal (n = 48) caregivers. Iterative feedback was gathered from rehabilitation inpatients during ongoing interactions and via post-discharge exit questionnaires, from informal caregivers via one-on-one interviews, and from formal caregivers via series of focus groups at various phases throughout the design process. Three main themes emerged from the analysis: (1) being individualized and user friendly (i.e., developing an app that is simple and easy to use to facilitate universal uptake), (2) targeting goals to promote self-management (i.e., adopting self-management skills relative to personal goals and confidence), and (3) increasing participation and support-seeking to facilitate lifestyle change (i.e., encouraging leisure activities to facilitate community integration). Key stakeholder perspectives contributed to the development of a self-management mobile app that will be evaluated in future research.

With decreasing inpatient lengths of stay following spinal cord injury (SCI), newly injured patients may be discharged into the community without the self-management skills needed to prevent secondary conditions. A mobile app was developed to facilitate self-management skills following SCI in the inpatient rehabilitation and early community settings. The objective of this study was to explore patients’ perspectives on the usability of this self-management app. A mixed-methods study design was implemented. The app was trialed at a local rehabilitation centre with 20 inpatient participants who experienced a SCI. They received mobile app training sessions throughout their inpatient rehabilitation. A thematic analysis was performed on qualitative data from post-discharge exit questionnaires and researchers’ field notes. Quantitative data (in the form of participants’ tool usage data and self-reported system usability scale scores) were collected at discharge and 3 months post-discharge. Three main themes emerged from the qualitative analysis: (1) being accessible to users (i.e., being easy to adopt and compatible with assistive technologies), (2) being intuitive to navigate (i.e., incorporating a simple app layout and a system of alert notifications), and (3) offering users flexibility (i.e., providing users with control over their data). The mobile app received above average mean system usability scale scores, both at discharge (78.1/100) and 3 months post-discharge (71.6/100). Given that participants found the app acceptable for use in inpatient rehabilitation and following discharge into the community, further testing is warranted to explore its efficacy in preventing secondary complications.

Most people with spinal cord injury will develop secondary complications with potentially devastating consequences. Self-management is a key prevention strategy for averting the development of secondary complications and their recurrence. Several studies have shown that self-management programs improve self-management behaviors and health outcomes in individuals living with chronic conditions such as asthma, diabetes, hypertension, and arthritis. Given the burgeoning health care costs related to secondary complications, we developed an alternative electronic health-based implementation to facilitate the development of self-management skills among people with spinal cord injury. This study aims to evaluate the efficacy of a self-management app in spinal cord injury populations. The primary outcome is attainment of self-selected, self-management goals. Secondary outcomes include increases in general and self-management self-efficacy and reductions in self-reported health events, health care utilization, and secondary complications related to spinal cord injury. This study also aims to explore how the intervention was implemented and how the app was experienced by end users. This study will employ a mix of qualitative and quantitative methods. The quantitative portion of our study will involve a rater-blinded, randomized controlled trial with a stepped wedge design (ie, delayed intervention control group). The primary outcome is successful goal attainment, and secondary outcomes include increases in self-efficacy and reductions in self-reported health events, health care utilization, and secondary conditions related to spinal cord injury. The qualitative portion will consist of semistructured interviews with a subsample of the participants. We expect that the mobile self-management app will help people with spinal cord injury to attain their self-management goals, improve their self-efficacy, reduce secondary complications, and decrease health care utilization. If the results are positive, this study will produce credible new knowledge describing multiple outcomes that people with spinal cord injury realize from an app-based self-management intervention and support its implementation in clinical practice. ClinicalTrials.gov NCT03140501; http://clinicaltrials.gov/ct2/show/NCT03140501 (Archived by WebCite at http://www.webcitation.org/73Gw0ZlWZ). PRR1-10.2196/11069.

Our research team developed a mobile application (app) to facilitate health-related self-management behaviors for secondary conditions among individuals with spinal cord injury (SCI). To facilitate mobile app adoption and ongoing use into the community, it is important to understand potential users' expectations and needs. The primary objective of this study was to explore user expectations of a mobile app intervention designed to facilitate self-management behavior among individuals with SCI. Data were collected via one-on-one, semi-structured interviews with a subsample of 20 community-dwelling participants enrolled in a larger, clinical trial. Analysis of the transcripts was undertaken using a six-phase process of thematic analysis. Our analysis identified three main themes for expectations of the mobile app intervention. The first theme, identified participants' expectation of being able to improve their psychological, behavioral, and physical health outcomes and reduce associated secondary conditions. The second theme, , identified participants' interest in exploring the functionality of the app and its ability to promote new experiences in health management. The third theme, , identified participants' desire to improve their understanding of their health and the expectation for the app to facilitate social engagement with others in the community. By exploring end-users' expectations, these findings may have short-term effects on improving continued mobile health app use among SCI populations and long-term effects on informing future development of mobile app interventions among chronic disease populations.