Premature hair greying in patients with pulmonary fibrosis and relatives is suggestive of pathogenic variants in telomere related genes

Résumé fourni par la source

Extract Dyskeratosis congenita is a rare syndrome diagnosed by the mucocutaneous triad of oral leukoplakia, nail dysplasia and abnormal skin pigmentation or by the presence of two components of the triad and bone marrow failure [1]. X-linked dyskeratosis congenita was the first telomere biology disorder (TBD) dissected at the genetic level with the identification of pathogenic variants in DKC1 [2]. Subsequently TERT and TERC, two other telomere related genes (TRGs), were implicated in TBD and familial pulmonary fibrosis (PF) [3]. Since then more than 20 TRGs have been associated with TBD including familial PF [4]. Pathogenic variants in TRGs disrupt telomere homeostasis, contributing to bone marrow failure, liver and lung disease, and other conditions associated with TBD [4]. Among patients with PF, a personal or family history of hematologic or hepatic conditions suggestive of TBD has been linked to a higher prevalence of pathogenic variants in TRGs compared to PF patients without such extrapulmonary features [5]. Pathogenic variants in TRG have been associated with a worse prognosis in PF and may influence therapeutic decision-making, particularly in the context of lung transplantation [6]. Patients carrying TRG pathogenic variants are at increased risk of hematological complications and infections, including CMV, following transplantation, especially when exposed to immunosuppressive and cytotoxic therapies [7].