UBA2 variants underlie a recognizable syndrome with variable aplasia cutis congenita and ectrodactyly.

PURPOSE: The human chromosome 19q13.11 deletion syndrome is associated with a variable phenotype that includes aplasia cutis congenita (ACC) and ectrodactyly as specific features. UBA2 (ubiquitin-like modifier-activating enzyme 2) lies adjacent to the minimal deletion overlap region. We aimed to define the UBA2-related phenotypic spectrum in humans and zebrafish due to sequence variants and to establish the mechanism of disease. METHODS: Exome sequencing was used to detect UBA2 sequence variants in 16 subjects in 7 unrelated families. uba2 loss of function was modeled in zebrafish. Effects of human missense variants were assessed in zebrafish rescue experiments. RESULTS: Seven human UBA2 loss-of-function and missense sequence variants were detected. UBA2-phenotypes included ACC, ectrodactyly, neurodevelopmental abnormalities, ectodermal, skeletal, craniofacial, cardiac, renal, and genital anomalies. uba2 was expressed in zebrafish eye, brain, and pectoral fins; uba2-null fish showed deficient growth, microcephaly, microphthalmia, mandibular hypoplasia, and abnormal fins. uba2-mRNAs with human missense variants failed to rescue nullizygous zebrafish phenotypes. CONCLUSION: UBA2 variants cause a recognizable syndrome with a wide phenotypic spectrum. Our data suggest that loss of UBA2 function underlies the human UBA2 monogenic disorder and highlights the importance of SUMOylation in the development of affected tissues.

Robot-Assisted Laparoscopic Distal Ureteroureterostomy for Distal Benign Ureteral Strictures with Long-Term Follow-Up.

Objectives: To demonstrate feasibility of robot-assisted laparoscopic (RAL) ureteroureterostomy (UU) for benign distal ureteral strictures (DUS) in our robotic reconstruction series with long-term follow-up. Patients and Methods: In a retrospective review of our prospectively maintained RAL ureteral reconstruction database, we followed patients between June 2012 and February 2019 who underwent a UU for DUS. In addition to patient demographics, we recorded the etiology, stricture length, and recurrence rates. Recurrence was defined as findings of recurrent or persistent obstruction by postoperative mercaptoacetyltriglycine diuretic renal scan or the need for additional intervention with ureteral drainage or revisional surgery. Results: We identified 22 patients who underwent a RAL-UU for DUS of benign etiologies. Median age was 42 years (interquartile range [IQR] 39-57) and 20 of 22 patients (90.1%) were women. Median stricture length was 1.5 cm (IQR 1-2). Iatrogenic surgical injury was noted in 16 patients (73%). All ureteral reconstruction was performed using RAL. Postoperative imaging consisted of renal ultrasonography, diuretic renal scan, or cross-sectional radiology within 3 months of the index operation. Further imaging was dependent on clinical judgment. Twenty patients (90.1%) had success with median follow-up time of 54.6 months with two recurrences necessitating RAL ureteroneocystostomy (UNC). Conclusion: RAL-UU for DUS is technically viable and shows promising efficacy in properly selected patients. This technique may serve a niche for preserving the natural anatomical drainage of the bladder and ureter in addition to obviating the sequela of vesicoureteral reflux as seen in UNC.

Multiple brain metastases in a patient with ypT0N0 micropapillary urothelial carcinoma of the bladder.

Radical cystectomy (RC) after neoadjuvant chemotherapy (NAC) is the gold standard for management of muscle-invasive bladder cancer (MIBC). Patients without residual tumor at the time of extirpative surgery (ypT0) have excellent prognosis. Distant metastases in this population are rare. We present a unique case of a patient with ypT0N0 urothelial carcinoma (UC) with rapid development of metastasis to the brain.