Abstract
Background: Mutations in telomere-related genes (TRGs) are the main cause of monogenic familial pulmonary fibrosis. Dyskerin, encoded by the X-localised gene DKC1, is involved in telomere maintenance.
Methods: This retrospective study aimed to further characterise the pulmonary phenotype of DKC1-deficient patients with pulmonary fibrosis identified between 2010 and 2025 in our laboratory.
Results: We reported eight, as yet undescribed, to our knowledge, probands affected by pulmonary fibrosis associated with X-linked DKC1 deficiency. The median age at interstitial lung disease (ILD) diagnosis was 47 years. Four had idiopathic pulmonary fibrosis, two unclassifiable fibrosis, one idiopathic nonspecific interstitial pneumonia and one unknown. All patients displayed ectodermal abnormalities (premature hair greying, nail dystrophies, reticulated hyper- or hypopigmentation, tooth abnormalities and oral leukoplasia). Haematological abnormalities were found in four patients. Seven patients died during follow-up and one patient received a transplant. Median survival after ILD diagnosis was 22 months (range 3-81 months).
Conclusions: Compared with patients with pulmonary fibrosis associated with other TRG variants, those with pulmonary fibrosis associated with X-linked recessive DKC1 variants are younger and have a shorter survival time. Early identification and referral of these patients to an expert transplantation centre should be considered.