Gelsolin dysfunction causes photoreceptor loss in induced pluripotent cell and animal retinitis pigmentosa models.

Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) cause X-linked RP (XLRP), an untreatable, inherited retinal dystrophy that leads to premature blindness. RPGR localises to the photoreceptor connecting cilium where its function remains unknown. Here we show, using murine and human induced pluripotent stem cell models, that RPGR interacts with and activates the actin-severing protein gelsolin, and that gelsolin regulates actin disassembly in the connecting cilium, thus facilitating rhodopsin transport to photoreceptor outer segments. Disease-causing RPGR mutations perturb this RPGR-gelsolin interaction, compromising gelsolin activation. Both RPGR and Gelsolin knockout mice show abnormalities of actin polymerisation and mislocalisation of rhodopsin in photoreceptors. These findings reveal a clinically-significant role for RPGR in the activation of gelsolin, without which abnormalities in actin polymerisation in the photoreceptor connecting cilia cause rhodopsin mislocalisation and eventual retinal degeneration in XLRP.Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) cause retinal dystrophy, but how this arises at a molecular level is unclear. Here, the authors show in induced pluripotent stem cells and mouse knockouts that RPGR mediates actin dynamics in photoreceptors via the actin-severing protein, gelsolin.

Complex regional pain syndrome in children: a systematic review of clinical features and movement disorders.

AIM: To ascertain clinical features of complex regional pain syndrome (CRPS) in children with a focus on movement disorders. METHODS: all publications with original data on children with CRPS were assessed. Data were tabulated and descriptive statistics were applied. RESULTS: One population-based study and nine clinic-based studies provided data on demographic and clinical characteristics of childhood CRPS. Mean age of onset was 12.5 years and 85% of patients were females (risk ratio: 1.70; 95% CI: 1.54-1.88). History of trauma in 71% and the lower limbs were affected in 75% of patients. A secondary site involvement was present in 15%. Movement disorders and dystonia were reported in 30% of children. CONCLUSION: Majority of cases of CRPS in children are females with mean age of 12.5 years. Movement disorders (mainly dystonia) affect at least one in three children with CRPS.

Complex regional pain syndrome in children: incidence and clinical characteristics.

OBJECTIVE: To study the clinical and epidemiological characteristics of complex regional pain syndrome (CRPS) in children. PATIENTS AND METHODS: All children and adolescents under 16 years of age with a new diagnosis of CRPS who were reported to the Scottish Paediatric Surveillance Unit were included. Patients' recruitment ran between 1 November 2011 and 31 October 2015. Information was collected on patients' demography, clinical features, investigations, management and impact of disease on child and family. The diagnosis of CRPS was made on fulfilling the clinical criteria of the International Association for the Study of Pain. RESULTS: 26 cases of CRPS were reported over 4 years, giving a minimum estimated incidence of 1.16/100 000 (95% CI 0.87 to 1.44/100 000) children 5-15 years of age. Nineteen patients were female (73%) and mean age at diagnosis was 11.9 (range 5.5-15.4 years). The median interval between onset of symptoms and diagnosis was 2 months (range 1-12). The majority of children have single site involvement, with legs been more often affected than arms and the right side is more often affected than the left. There was a clear trauma at onset of the illness in 19 children and possible nerve injury in one. All investigations were normal and several treatment modalities were used with variable success. The disease had significant impacts on the patients' education and family lives. CONCLUSIONS: The estimated incidence of CRPS is 1.2/100 000 children 5-15 years old. The diagnosis of CRPS is often delayed. CRPS has a significant impact on children and their families.