A Noncanonical Splice Variant in RTEL1 Responsible for Familial Pulmonary Fibrosis

Abstract

We report a family with multiple individuals with pulmonary fibrosis of variable severity, age of onset, and clinical characteristics. Initial clinical investigations of the proband identified a splice-region variant of uncertain significance (VUS; NM_032957.4: c.3181 + 3A>C) in RTEL1. Telomere studies showed shortened telomeres (10th percentile). Family studies and functional analyses (mRNA studies and Western blot) were performed to reinterpret the pathogenicity of the variant, allowing for predictive testing of family members and changes to medical management, thus demonstrating the importance of these tools in variant interpretation and the value of predictive testing for at-risk family members.

Keywords: familial pulmonary fibrosis; interstitial lung disease; regulator of telomere elongation helicase 1.