A novel mutation (p.Y24N) in NHP2 leads to idiopathic pulmonary fibrosis and lung carcinoma chronic obstructive lung disease by disrupting the expression and nucleocytoplasmic localization of NHP2

Idiopathic pulmonary fibrosis (IPF) is a kind of chronic interstitial lung disease and can be caused by mutations in NHP2 ribonucleoprotein (NHP2), a component of the telomerase complex. We identified a novel mutation (c.70 T > A/p.Y24N) in NHP2 in a Chinese family with IPF, chronic obstructive lung disease and lung carcinoma. A functional study confirmed that this mutation can disrupt the expression and nucleocytoplasmic localization of NHP2, further decrease the expression of Dyskerin Pseudouridine Synthase 1 and Regulator of Telomere Elongation Helicase 1, and reduce the length of telomeres. Our study expanded the mutation and clinical spectrum of NHP2 deficiency.