GABBR2 mutations determine phenotype in rett syndrome and epileptic encephalopathy.

OBJECTIVE: Rett syndrome (RTT) and epileptic encephalopathy (EE) are devastating neurodevelopmental disorders with distinct diagnostic criteria. However, highly heterogeneous and overlapping clinical features often allocate patients into the boundary of the two conditions, complicating accurate diagnosis and appropriate medical interventions. Therefore, we investigated the specific molecular mechanism that allows an understanding of the pathogenesis and relationship of these two conditions. METHODS: We screened novel genetic factors from 34 RTT-like patients without MECP2 mutations, which account for ∼90% of RTT cases, by whole-exome sequencing. The biological function of the discovered variants was assessed in cell culture and Xenopus tropicalis models. RESULTS: We identified a recurring de novo variant in GABAB receptor R2 (GABBR2) that reduces the receptor function, whereas different GABBR2 variants in EE patients possess a more profound effect in reducing receptor activity and are more responsive to agonist rescue in an animal model. INTERPRETATION: GABBR2 is a genetic factor that determines RTT- or EE-like phenotype expression depending on the variant positions. GABBR2-mediated γ-aminobutyric acid signaling is a crucial factor in determining the severity and nature of neurodevelopmental phenotypes. Ann Neurol 2017;82:466-478.

Effect of educational preparation on the accuracy of linear growth measurement in pediatric primary care practices: results of a multicenter nursing study.

Consistently monitoring a child's linear growth is one of the least invasive, most sensitive tools to identify normal physiologic functioning and a healthy lifestyle. However, studies, mostly from the United Kingdom, indicate that children are frequently measured incorrectly. Inaccurate linear measurements may result in some children having undetected growth disorders whereas others with normal growth being referred for costly, unwarranted specialty evaluations. This study presents the secondary analysis of a primary study that used a randomized control study design to demonstrate that a didactic educational intervention resulted in significantly more children being measured accurately within eight pediatric practices. The secondary analysis explored the influence of the measurer's educational level on the outcome of accurate linear measurement. Results indicated that RNs were twice as likely as non-RNs to measure children accurately.