1. Berkel S, Tang W, Trevino M, Vogt M, Obenhaus HA, Gass P, Scherer SW, Sprengel R, Schratt G, Rappold GA. {{Inherited and de novo SHANK2 variants associated with autism spectrum disorder impair neuronal morphogenesis and physiology}}. {Hum Mol Genet}. 2012 Jan 15;21(2):344-57.
Mutations in the postsynaptic scaffolding gene SHANK2 have recently been identified in individuals with autism spectrum disorder (ASD) and intellectual disability. However, the cellular and physiological consequences of these mutations in neurons remain unknown. We have analyzed the functional impact caused by two inherited and one de novo SHANK2 mutations from ASD individuals (L1008_P1009dup, T1127M, R462X). Although all three variants affect spine volume and have smaller SHANK2 cluster sizes, T1127M additionally fails to rescue spine volume in Shank2 knock-down neurons. R462X is not able to rescue spine volume and dendritic branching and lacks postsynaptic clustering, indicating the most severe dysfunction. To demonstrate that R462X when expressed in mouse can be linked to physiological effects, we analyzed synaptic transmission and behavior. Principal neurons of mice expressing rAAV-transduced SHANK2-R462X present a specific, long-lasting reduction in miniature postsynaptic AMPA receptor currents. This dominant negative effect translates into dose-dependent altered cognitive behavior of SHANK2-R462X-expressing mice, with an impact on the penetrance of ASD.
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2. Gabos PG, Inan M, Thacker M, Borkhu B. {{Spinal fusion for scoliosis in rett syndrome with an emphasis on early postoperative complications}}. {Spine}. 2012 Jan 15;37(2):E90-4.
STUDY DESIGN.: Retrospective case-control study. OBJECTIVE.: To examine the postoperative complications of posterior spinal fusion in a population of patients with Rett syndrome (RS). SUMMARY OF BACKGROUND DATA.: Scoliosis is a common feature of RS, a progressive neurologic disorder affecting almost exclusively females. Despite this, there is little published information regarding the surgical treatment of scoliosis in this disorder. METHODS.: Sixteen consecutive female patients with RS treated by posterior spinal fusion and unit rod instrumentation for progressive scoliosis between 1995 and 2003 were evaluated. Only patients with a minimum of 2-year follow-up were included. Preoperative medical conditions and postoperative complications were recorded. As a control group, we randomly selected 32 spastic quadriplegic patients who underwent the identical procedure during the same time period, selected from our database and matched according to age, level of neurologic impairment, and medical complexity. RESULTS.: There was a high rate of early medical complications in the RS patients, with 28 major and 37 minor complications. Only 1 patient did not have a major medical complication, and every patient had at least 1 minor gastrointestinal and/or respiratory complication. Major respiratory complications occurred in 10 patients (63%) and comprised 61% of all major complications. Major gastrointestinal complications occurred in 6 patients (37%) and comprised 21% of all major complications. Other major complications included disseminated intravascular coagulopathy (1 patient), subacute bacterial endocarditis (1 patient), sacral decubiti requiring surgical debridement (2 patients), and extensive bilateral heterotopic ossification of the hips (1 patient). There were no cases of instrumentation failure, pseudarthrosis, deep infection, or need for rod revision. Postoperative complication scores were similar to those in patients with spastic quadriplegic pattern cerebral palsy. CONCLUSION.: Spinal fusion for scoliosis in RS can give a satisfactory technical result, but a high rate of early postoperative medical problems should be anticipated.
