BACKGROUND Exome sequencing is emerging as a first-line diagnostic method in some clinical disciplines, but its usefulness has yet to be examined for most constitutional disorders in adults, including chronic kidney disease, which affects more than 1 in 10 persons globally. METHODS We conducted exome sequencing and diagnostic analysis in two cohorts totaling 3315 patients with chronic kidney disease. We assessed the diagnostic yield and, among the patients for whom detailed clinical data were available, the clinical implications of diagnostic and other medically relevant findings. RESULTS In all, 3037 patients (91.6%) were over 21 years of age, and 1179 (35.6%) were of self-identified non-European ancestry. We detected diagnostic variants in 307 of the 3315 patients (9.3%), encompassing 66 different monogenic disorders. Of the disorders detected, 39 (59%) were found in only a single patient. Diagnostic variants were detected across all clinically defined categories, including congenital or cystic renal disease (127 of 531 patients [23.9%]) and nephropathy of unknown origin (48 of 281 patients [17.1%]). Of the 2187 patients assessed, 34 (1.6%) had genetic findings for medically actionable disorders that, although unrelated to their nephropathy, would also lead to subspecialty referral and inform renal management. CONCLUSIONS Exome sequencing in a combined cohort of more than 3000 patients with chronic kidney disease yielded a genetic diagnosis in just under 10% of cases. (Funded by the National Institutes of Health and others.)

Purpose: Recruitment of participants from diverse backgrounds is crucial to the generalizability of genetic research, but has proven challenging. We retrospectively evaluated recruitment methods used for a study on return of genetic results. Methods: The costs of study design, development, and participant enrollment were calculated, and the characteristics of the participants enrolled through the seven recruitment methods were examined. Results: A total of 1118 participants provided consent, a blood sample, and questionnaire data. The estimated cost across recruitment methods ranged from $579 to $1666 per participant and required a large recruitment team. Recruitment methods using flyers and staff networks were the most cost-efficient and resulted in the highest completion rate. Targeted sampling that emphasized the importance of Latino/a participation, utilization of translated materials, and in-person recruitments contributed to enrolling a demographically diverse sample. Conclusions: Although all methods were deployed in the same hospital or neighborhood and shared the same staff, each recruitment method was different in terms of cost and characteristics of the enrolled participants, suggesting the importance of carefully choosing the recruitment methods based on the desired composition of the final study sample. This analysis provides information about the effectiveness and cost of different methods to recruit adults for genetic research.

Alopecia areata (AA) is a common autoimmune disease and it is challenging to predict which patients will have severe disease. The purpose of this retrospective study was to identify comorbidities in children enrolled in the National Alopecia Areata Registry. Atopic dermatitis was more common in patients with severe AA than in those with mild disease. The most common autoimmune comorbidities were vitiligo, psoriasis, thyroid disease, and juvenile idiopathic arthritis.

Purpose: Patients with prostate cancer (PCa) treated with apalutamide frequently develop rash. We aim to characterize apalutamide-related dermatological adverse events (dAEs) and management. Materials and Methods: We assessed 303 patients with PCa treated with apalutamide. DAE frequency and time to onset were calculated and clinicopathological features and management described. Associations between dAE occurrence and clinical trial participation, as well as abiraterone/prednisone exposure were detected using logistic regression models.Results: Seventy-one (23.4%) patients had all-grade dAE occurring at a median of 77 (IQR: 30e135) days post-exposure. Twenty (6.6%) dAE-related therapy interruptions included: 8 (2.6%) with dose maintained on rechallenge, 7 (2.3%) with dose reduction and 5 (1.7%) with discontinuation. Common dAEs were maculopapular rashes (33.8%) and xerosis (32.4%). Seven (77.8%) of 9 histological analyses of skin biopsies supported a drug reaction. No significant differences in laboratory hematological, hepatic and renal function were detected between dAE and no dAE cohorts. Most treated grade