Abstract Introduction Usher Syndrome Type I (UST1) is an autosomal recessive disorder subtype defined clinically by childhood-onset sensorineural hearing loss (SNHL) and retinitis pigmentosa (RP). The underlying genetic mutation contributing to the development of its clinical manifestations is caused by a defective protein subunit, myosin-VIIa, in cilia located in cochlear hair cells, photoreceptors, and retinal epithelium. Myosin-VIIa is present in other ciliated cells in the lungs, kidneys, and intestines. Prior literature suggests that myosin-VIIa defects in a variety of ciliated tissue may contribute to less commonly reported phenotypical variations in patients with UST1. We present a case of a patient with UST1 who developed adult-onset bronchiectasis, adding to the literature that ciliary dyskinesia due to Myosin-VIIa subunit abnormalities may rarely be present and cause a sinopulmonary phenotype in UST1. Case Description A 47-year-old female experienced childhood-onset SNHL and vision loss. She was diagnosed with RP at that time. At age 43, this patient began experiencing worsening productive cough and recurrent sinopulmonary infections. In 2022, she was diagnosed with bronchiectasis based on imaging and her clinical history. This patient presented to us in Bronchiectasis Clinic after a recent hospitalization for bronchiectasis exacerbation with symptoms of worsening dyspnea, increased sputum production, and declining pulmonary function. Our evaluation for other potential etiologies of bronchiectasis included testing for primary immunoglobulin deficiencies, nontuberculous mycobacteria, allergic bronchopulmonary aspergillosis and other fungal infections, parasitic infections, autoimmune disease, and cystic fibrosis, all which were negative. Her genetic testing was significant for the MYOZA gene mutation c.3795GA, homozygous (p.Met1265lle), which is a genetic variant consistent with UST1. She has a history of consanguinity in a primary relative, which likely explains her genetic inheritance of UST1. Discussion Cases of UST1 with associated bronchiectasis have been reported rarely in the literature; in these instances, defective mucociliary clearance was demonstrated in two patients with UST1. In another patient case, microscopic analysis of bronchial brushings exhibited ciliary aplasia in lung tissue. The genetic landscape for ciliary dyskinesias is continually expanding with evolutions in next generation sequencing. Ongoing discoveries of genetic variants and new or previously unrecognized genotype-phenotype correlations in ciliary dyskinesias are being increasingly identified. This patient case illustrates UST1 may rarely present clinically with evidence of ciliary disorder and adds to the growing clinical spectrum of ciliary dyskinesias. Additionally, this case emphasizes the need to identify rare genetic causes of bronchiectasis and ciliary dyskinesia to understand specific etiologies and guide future treatment developments. This abstract is funded by: None
O’Bryant et al. (Fri,) studied this question.