A novel RTEL1 nonsense variant in a case of familial pulmonary fibrosis: clinical description and genetic implications

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease, often linked to telomere-related gene (TRG) mutations in familial forms. Telomere biology disorders can also manifest with systemic features such as bone marrow failure and liver disease. We report a 72-year-old woman with a family history of pulmonary fibrosis and premature hair greying. The patient had a history of bronchopneumonia at age 20 and pulmonary tuberculosis at age 23. Genetic testing identified a novel heterozygous nonsense variant in Regulator of Telomere Elongation Helicase 1 (RTEL1) (NM_001283009.2:c.2962 C > 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. This case expands the mutational and clinical spectrum of RTEL1-associated interstitial lung diseases and underscores the importance of genetic testing in patients with familial pulmonary fibrosis.