ITSN1: a novel candidate gene involved in autosomal dominant neurodevelopmental disorder spectrum.

ITSN1 plays an important role in brain development. Recent studies in large cohorts of subjects with neurodevelopmental disorders have identified de novo variants in ITSN1 gene thereby suggesting that this gene is involved in the development of such disorders. The aim of this study is to provide further proof of such a link. We performed trio exome sequencing in a patient presenting autism, intellectual disability, and severe behavioral difficulties. Additional affected patients with a neurodevelopmental disorder harboring a heterozygous variant in ITSN1 (NM_003024.2) were collected through a worldwide collaboration. All patients underwent detailed phenotypic and genetic assessment and data was collected and shared by healthcare givers. We identified ten novel patients from eight families with heterozygous truncating or missense variants in ITSN1 gene. In addition, four previously published patients from large meta-analysis studies were included. In total, 7/14 patients presented a de novo variant in ITSN1. All patients showed neurodevelopmental disorders from autism spectrum disorders (90%), intellectual disability (86%), and epilepsy (30%). We demonstrated that truncating variants are in the first half of ITSN1 whereas missense variants are clustered in C-terminal region. We suggest ITSN1 gene is involved in development of an autism spectrum disorder with variable additional neurodevelopmental deficiency, thus confirming the hypothesis that ITSN1 is important for brain development.

Variability in asthma quality and costs in children with different Medicaid insurance plans in Maricopa County.

OBJECTIVE: To describe the variation in asthma quality and costs among children with different Medicaid insurance plans. METHODS: We used 2013 data from the Center for Health Information and Research, which houses a database that includes individuals who have Medicaid insurance in Arizona. We analyzed children ages 2-17 years-old who lived in Maricopa County, Arizona. Asthma medication ratio (AMR, a measure of appropriate asthma medication use), outpatient follow-up within 2 weeks after asthma-related hospitalization (a measure of continuity of care), asthma-related hospitalizations, and all emergency department (ED) visits were the primary quality metrics. Direct costs were reported in 2013 $US dollars. We used one-way analysis of variance to compare the health plans for AMR and per member cost (total, ER, and hospital), and the chi-squared test for the outpatient follow-up measure. We used coefficient of variation to identify variation of each measure across all individuals in the study. RESULTS: In 2013, 90,652 children in Maricopa County were identified as having asthma. The average patient-weighted AMR for children with persistent asthma was 0.35, well short of the goal of ≥0.70, and only 36% of hospitalized asthma patients had outpatient follow-up within 2 weeks of hospitalization. AMR, total costs, and ED costs varied significantly (p <.0001) when comparing health plans while hospital costs and outpatient follow-up showed no significant variation. CONCLUSIONS: Targeting appropriate medication use for asthma may help reduce variation, improve outcomes, and increase healthcare value for children with asthma and Medicaid insurance in the US.