A Novel Rtel1 Nonsense Variant in a Case of Familial Pulmonary Fibrosis

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease, often linked to telomere-related gene (TRG) mutations in familial forms. Case presentation We report a 72-year-old woman with a family history of pulmonary fibrosis and premature hair greying. Genetic testing identified a novel heterozygous nonsense variant in Regulator of Telomere Elongation Helicase 1 (RTEL1) (NM_001283009.2:c.2962C > T; p.Gln988Ter). This variant introduces a premature stop codon, likely leading to loss of function. The variant, absent from major population databases, was classified as “likely pathogenic” according to ACMG criteria. RTEL1 encodes a DNA helicase essential for DNA replication and telomere maintenance, and its disruption contributes to epithelial cell dysfunction in pulmonary fibrosis. Conclusion This case expands the mutational spectrum of RTEL1-associated interstitial lung diseases and underscores the importance of genetic testing in patients with familial pulmonary fibrosis.