Molecular characterization of an intronic RNASEH2B variant in a patient with Aicardi-Goutières syndrome.

Aicardi-Goutières syndrome (AGS) is a progressive multisystem disorder including encephalopathy with significant impacts on intellectual and physical abilities. An early diagnosis is becoming ever more crucial, as targeted therapies are emerging. A deep understanding of the molecular heterogeneity of AGS can help guide the early diagnosis and clinical management of patients, and inform recurrence risks. Here, we detail the diagnostic odyssey of a patient with an early presentation of AGS. Exome and genome sequencing detected an intronic RNASEH2B variant missed in a conventional leukodystrophy NGS gene panel. RNA studies demonstrated that a c.322-17 A > G variant affected splicing and caused 16-nucleotide intronic retention in the RNASEH2B transcript, introducing an out-of-frame early termination codon. RNASEH2B expression in the patient's blood was reduced when compared to controls. Our study highlights the pathogenicity of this intronic variant and the importance of its inclusion in variant assessment.

Characteristics of youth seeking emergency care for assault injuries.

OBJECTIVE: To characterize youth seeking care for assault injuries, the context of violence, and previous emergency department (ED) service utilization to inform ED-based injury prevention. METHODS: A consecutive sample of youth (14-24) presenting to an urban ED with an assault injury completed a survey of partner violence, gun/knife victimization, gang membership, and context of the fight. RESULTS: A total of 925 youth entered the ED with an assault injury; 718 completed the survey (15.4% refused); 730 comparison youth were sampled. The fights leading to the ED visit occurred at home (37.6%) or on streets (30.4%), and were commonly with a known person (68.3%). Fights were caused by issues of territory (23.3%) and retaliation (8.9%); 20.8% of youth reported substance use before the fight. The assault-injured group reported more peer/partner violence and more gun experiences. Assault-injured youth reported higher past ED utilization for assault (odds ratio [OR]: 2.16) or mental health reasons (OR: 7.98). Regression analysis found the assault-injured youth had more frequent weapon use (OR: 1.25) and substance misuse (OR: 1.41). CONCLUSIONS: Assault-injured youth seeking ED care report higher levels of previous violence, weapon experience, and substance use compared with a comparison group seeking care for other complaints. Almost 10% of assault-injured youth had another fight-related ED visit in the previous year, and ~5% had an ED visit for mental health. Most fights were with people known to them and for well-defined reasons, and were therefore likely preventable. The ED is a critical time to interact with youth to prevent future morbidity.