Adult male patients with DKC1 mutations present early onset pulmonary fibrosis and severe prognosis

Mutations in telomere related genes (TRGs) are the main cause of monogenic familial pulmonary fibrosis. Dyskerin, encoded by the X-localized gene DKC1 , is involved in telomere maintenance. This retrospective study aimed to further characterize the pulmonary phenotype of DKC1 deficient patients with pulmonary fibrosis identified between 2010 and 2025 in our laboratory. We reported eight, yet undescribed, probands affected by pulmonary fibrosis associated to X-linked DKC1 deficiency. The median age at interstitial lung disease (ILD) diagnosis was 47 years-old. Four had idiopathic pulmonary fibrosis, two unclassifiable fibrosis, one idiopathic non-specific interstitial pneumonia and one unknown. All patients displayed ectodermal abnormalities (premature hair greying, nail dystrophies, reticulated hyper- or hypopigmentation, tooth abnormalities and oral leukoplasia). Hematological abnormalities were found in four patients. Seven patients died during follow-up and one patient was transplanted. Median survival after ILD diagnosis was 22 months (min – max 3–81 months). Compared to patients with pulmonary fibrosis associated with other TRG variants, those with pulmonary fibrosis linked to X-linked recessive DKC1 variants are younger and have shorter survival. Early identification and referral of these patients to an expert transplantation center should be considered. Short abstract X-linked recessive DKC1 deficiency is associated with rapidly progressive pulmonary fibrosis and ectodermal involvement. Early identification and referral of these patients to an expert transplantation center should be considered.