HPS4 bi-allellic ultra-rare variants in Hermansky-Pudlak syndrome pulmonary fibrosis patients in Greece, Cyprus and Türkiye
Bildiriler > Özet Bildiri
Yazarlar: Effrosyni D. Manali, Ibrahima Ba, Lykourgos Kolilekas, Vincent Michaud, Frangiskos Frangopoulos, Paschalis Steiropoulos, Tonia Adamide, Nesrin MOĞULKOÇ BISHOP, Andriana I Papaioannou, Gilmaz Batzak, Olga Katsarou, Ioanna Anastasopoulou, Maria Kallieri, Burak Gökçe, Raphael Borie, Apostolos Malatras, Dionysios Fanidis, Lidwine Wemeau, Elvira-Markela Antonogiannaki, Vasiliki Apollonatou, Bruno Crestani, Resat Cinar, Constantinos Deltas, Benoît Arveiler, Caroline Kannengiesser, Spyros A Papiris
Rare ILD/DPLD, , , Uluslararası, Özet Bildiri, ss PA6124-PA6124
DOI: 10.1183/13993003.congress-2025.pa6124
Özet
Background: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder. HPS pulmonary fibrosis (PF) is highly penetrant and associated mainly to HPS-1 mutations lacking treatment. HPS-4 is extremely rare. Aim: to characterize HPS-PF in Greece, Cyprus, Türkiye. Methods: retrospective study from April 2022-October 2024. Epidemiological, clinical, functional, genetic data were analyzed. Results: 22 HPS4 homozygous patients (12 Greece, 9 Cyprus, 1 Türkiye) were reported. Genetic analysis disclosed 3 HPS4 ultra-rare variants [c.649C>T, p.(Arg217*); c.1090C>T, p.(Gln364*); c.239_240del, p.Leu80GlnfsTer7] respectively attributed to founder effect. Eleven patients had PF (55% familial): median (years) (IQR) age at diagnosis 50 (44-61), 64% male, 73% non-smokers, median %-predicted FVC, DLCO 89 (73-101), 66 (40-74) respectively; All patients had oculocutaneous albinism at birth (91% familial), 91% bleeding-diathesis, 27% hearing loss, 18% colitis, 9% renal disease. HRCT pattern was indeterminate for UIP in 73%. At diagnosis, 36% of patients were symptomatic, 64% were identified by screening. Long-term oxygen was prescribed in 18%, antifibrotics in 18%. 27% have died. Non-survivors were more likely ever-smokers (p=0.004), on oxygen (p=0.011), symptomatic (p=0.007) with worse functional status (p=0.02) and fibrosis (p=0.04). Conclusion: In Greece, Cyprus and Türkiye HPS-PF is related to 3 ultra-rare HPS4 variants. HPS4-PF develops at a younger age, relates with functional impairment and extrapulmonary manifestations of variable severity. Smoking negatively affects survival. Screening in high-risk populations could permit early diagnosis and improve outcome.