York platelet syndrome is a CRAC channelopathy due to gain-of-function mutations in STIM1.

Store-operated Ca(2+) entry is the major route of replenishment of intracellular Ca(2+) in animal cells in response to the depletion of Ca(2+) stores in the endoplasmic reticulum. It is primarily mediated by the Ca(2+)-selective release-activated Ca(2+) (CRAC) channel, which consists of the pore-forming subunits ORAI1-3 and the Ca(2+) sensors, STIM1 and STIM2. Recessive loss-of-function mutations in STIM1 or ORAI1 result in immune deficiency and nonprogressive myopathy. Heterozygous gain-of-function mutations in STIM1 cause non-syndromic myopathies as well as syndromic forms of miosis and myopathy with tubular aggregates and Stormorken syndrome; some of these syndromic forms are associated with thrombocytopenia. Increased concentration of Ca(2+) as a result of store-operated Ca(2+) entry is essential for platelet activation. The York Platelet syndrome (YPS) is characterized by thrombocytopenia, striking ultrastructural platelet abnormalities including giant electron-opaque organelles and massive, multilayered target bodies and deficiency of platelet Ca(2+) storage in delta granules. We present clinical and molecular findings in 7 YPS patients from 4 families, demonstrating that YPS patients have a chronic myopathy associated with rimmed vacuoles and heterozygous gain-of-function STIM1 mutations. These findings expand the phenotypic spectrum of STIM1-related human disorders and define the molecular basis of YPS.

Participant Perspectives on the Implementation of a School-Linked Text-Message Intervention to Improve Pediatric Asthma Medication Adherence.

Background: Poor adherence to inhaled corticosteroids (ICS) is a significant challenge in pediatric asthma, contributing to health inequities. Text-message reminders for ICS therapy are an evidence-based approach that improves pediatric asthma medication adherence, yet has not been widely adopted into practice, partly due to lack of (1) participant input on design and implementation and (2) use of sustainable community linkages. Remote Asthma Link™ (RAL) seeks to fill this gap as a school-linked text-message intervention wherein parents of children with poorly controlled asthma received daily, 2-way text-message reminders for preventive inhaler use. Responses were shared with school nurses who conducted remote check-ins with families. Enrolled children, largely from underserved backgrounds, experienced improvements in medication adherence and asthma health outcomes. While initial results were promising, we have yet to elicit participant input to refine the protocol for more widespread implementation. Objective: Examine participant perspectives on barriers and facilitators of RAL implementation. Methods: Semistructured interviews were conducted May-June 2022 with intervention participants: 10 parents, 7 school nurses, and 4 pediatric providers (n = 21) until thematic saturation was reached. Interview transcripts were coded using thematic analysis. Results: Several facilitators for RAL implementation were identified, including ease of use and accessibility, personal connection to the school nurse, and receipt of a visual notification for habit formation. Barriers included challenges with school nurses reaching parents, poor understanding of program expectations, and lack of reimbursement structure. Participant-proposed solutions to barriers included utilizing alternate communication methods (eg, social media), educational sessions, and meeting with payors to consider reimbursement models. Conclusion: RAL is a school-linked text-message intervention demonstrating promise in improving outcomes and equity in asthma care. Key implementation facilitators, barriers, and proposed solutions will inform protocol adaptations to promote successful implementation of this and other text-message interventions into clinical practice.