2026-06-22 | Novel pathogenic variant in ARMC4 identified by whole exome sequencing in a Turkish family with primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder affecting approximately 1:15,000 to 1:30,000 individuals. It is characterized by upper and lower respiratory diseases, otitis media, congenital heart defects, situs inversus, infertility in males, and hydrocephalus. Whole-exome sequencing (WES) has become an important tool for identifying novel pathogenic variants associated with PCD. Trio-based WES was performed in two Turkish siblings with clinically suspected PCD born to healthy consanguineous parents. Candidate variants were validated by Sanger sequencing and functionally assessed using immunofluorescence (IF) analysis of respiratory cilia obtained by nasal brushing biopsy. A novel homozygous frameshift pathogenic variant in ARMC4 [c.324dupA; p.Arg109Thrfs*19] was identified in both affected siblings. IF analysis demonstrated absence of ARMC4 protein in the ciliary axonemes and distal loss of DNAH5, confirming the functional effect of the variant. These findings expand the mutational spectrum of ARMC4-associated PCD and highlight the importance of combining genetic and functional analyses for accurate diagnosis and variant interpretation in PCD.

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2026-06-15 | Sotatercept treatment in a patient with end-stage bronchiolitis obliterans syndrome after lung transplantation.

Bronchiolitis obliterans syndrome (BOS), the most common form of chronic lung allograft dysfunction after lung transplantation, is characterized by progressive small airway disease (SAD) and is associated with poor outcomes and limited therapeutic options. Sotatercept, an activin-signaling inhibitor approved for pulmonary arterial hypertension, has been associated with improvements in physiologic markers of SAD in patients with pulmonary hypertension. In this report, we describe a 55-year-old woman with primary ciliary dyskinesia status post bilateral lung transplantation who developed stage 3 BOS complicated by hypercapnic respiratory failure requiring mechanical ventilation. Following initiation of off-label sotatercept, she experienced rapid clinical and radiologic improvement, permitting transient liberation from mechanical ventilation before succumbing to progressive respiratory failure. Further study is required to assess the potential role for activin pathway modulation in advanced BOS.

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2026-06-01 | High-dose continuous infusion of piperacillin/tazobactam via elastomeric pump in a pediatric patient with Kartagener syndrome: pharmacokinetic target attainment and clinical outcome.

Multidrug-resistant Achromobacter xylosoxidans infections in pediatric patients with primary ciliary dyskinesia (PCD) often require prolonged intravenous therapy. We evaluated the pharmacokinetics of continuous infusion piperacillin/tazobactam (16 g/2 g daily) in a 13-year-old male with situs inversus and chronic otitis media transitioned from hospital-based electronic infusion to home-based Outpatient Parenteral Antimicrobial Therapy (OPAT) using elastomeric pumps. Plasma concentrations were measured by Therapeutic Drug Monitoring (TDM), and tissue exposure was estimated using conservative penetration coefficients. Drug concentrations consistently remained above the MIC (≤2 mg/L). During hospitalization, steady-state concentrations were stable (27.2-29.0 mg/L; CV 4.5%), whereas during OPAT they were higher and more variable (53.9-80.1 mg/L; CV 20.1%), consistent with the known non-linear delivery profiles of elastomeric devices. Despite this variability, TDM confirmed sustained supratherapeutic exposure, with estimated tissue concentrations remaining >5-fold above the MIC. Clinical resolution was achieved without adverse events, supporting the role of TDM-guided OPAT in difficult-to-treat infections.

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