Alien Registration- Breau, Elizabeth (Rumford, Oxford County)

https://digitalmaine.com/alien_docs/13591/thumbnail.jp

Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome

SPTBN1 mutations cause a neurodevelopmental syndrome characterized by intellectual disability, language and motor delays, autism, seizures and other features. The variants disrupt beta II-spectrin function and disturb cytoskeletal organization and dynamics. SPTBN1 encodes beta II-spectrin, the ubiquitously expressed beta-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal beta II-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays;mild to severe intellectual disability;autistic features;seizures;behavioral and movement abnormalities;hypotonia;and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect beta II-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of beta II-spectrin in the central nervous system

Alien Registration- Breau, Elizabeth (Rumford, Oxford County)

https://digitalmaine.com/alien_docs/13591/thumbnail.jp

The Pediatric American Pain Society Patient Outcomes Questionnaire (Pediatric APS-POQ): Development and Initial Psychometric Evaluation of a Brief and Comprehensive Measure of Pain and Pain Outcomes in Hospitalized Youth

Pediatric pain assessment in the hospital traditionally involves the patient\u27s self-report of pain intensity using a numeric rating scale, which does not capture the complexity of the pain experience. No valid, comprehensive measure of pain in hospitalized youth exists. This study was designed to develop and conduct initial psychometric testing of the Pediatric American Pain Society Patient Outcomes Questionnaire (Pediatric APS-POQ), a comprehensive patient-reported measure of pain and pain outcomes in hospitalized youth. A multidisciplinary group of pediatric pain researchers and clinicians collaborated to adapt the adult APS-POQ Revised to pediatrics, including a patient-report and parent proxy version. The adapted measures were administered to 218 pediatric inpatients (age M = 13.4 years, 56% female) and 214 of their parents (80% mothers) at 4 US children\u27s hospitals. The measure was feasible to administer within the inpatient setting and was acceptable and understandable to pediatric patients and their parents. Internal consistency was adequate for both patient-report and parent proxy (α = 0.77). Confirmatory factor analysis supported the following 6 domains, consistent with the adult measure: pain intensity, functional interference, emotional response, side effects, perceptions of care, and usual pain. Additional research is needed to further support the reliability and validity of this measure in diverse clinical populations. PERSPECTIVE: To reduce the impact of pain on hospitalized youth, pediatric pain assessment must move beyond ratings of pain intensity. The Pediatric APS-POQ provides a brief but comprehensive assessment of pain and pain outcomes in hospitalized children and adolescents, which will allow for greater individualization in hospital-based pain management and quality improvement purposes

Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome

SPTBN1 encodes βII-spectrin, the ubiquitously expressed β-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal βII-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of βII-spectrin in the central nervous system