TINF2 – Pulmonary Fibrosis

The shelterin component TINF2 is essential for telomere protection and maintenance. In a sporadic case, a heterozygous c.734C>A (p.Ser245Tyr) variant was detected in a 52-year-old woman presenting with progressive pulmonary fibrosis accompanied by panhypogammaglobulinemia (HP:0003139) and exertional dyspnea (HP:0002875) (PMID:27088026). Telomere length measured in peripheral blood was within normal limits, indicating telomere dysfunction independent of global shortening. No familial segregation was reported.

A subsequent study of five Greek patients with co-occurring idiopathic pulmonary fibrosis and myelodysplastic syndrome failed to identify pathogenic TINF2 variants (PMID:31409344), highlighting the rarity of this association. Functional assays of TINF2 variants have demonstrated telomere maintenance defects in bone marrow failure syndromes but have not been performed in pulmonary fibrosis models. Overall, evidence linking TINF2 to isolated pulmonary fibrosis is limited to a single proband, and replication in larger cohorts and mechanistic studies are required. Key take-home: TINF2 screening may be considered in unexplained pulmonary fibrosis with immunodeficiency or telomere syndrome features.

References

• Case reports in pulmonology • 2016 • TINF2 Gene Mutation in a Patient with Pulmonary Fibrosis. PMID:27088026
• Respiratory research • 2019 • Myelodysplastic syndromes and idiopathic pulmonary fibrosis: a dangerous liaison. PMID:31409344

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