Telomeres in Hermansky-Pudlak Syndrome pulmonary fibrosis

Authors

• C Han
• H Dorward
• T Franklin
• KJ O'Brien
• WA Gal
• MCV Malicdan
• BR Gochuico

Abstract

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by abnormal vesicle trafficking and defective biogenesis of lysosome-related organelles. There are ten different genetic types of HPS, including some with type-specific manifestations of disease. HPS types 1, 2, and 4 are associated with progressive pulmonary fibrosis. Patients with telomere disease, which is an autosomal dominant disorder characterized by short telomeres, can develop familial pulmonary fibrosis. The pathogenesis of pulmonary fibrosis is complex and incompletely understood. Given the high penetrance of pulmonary fibrosis in patients with HPS and telomere disease, we hypothesized that these disorders share a common underlying mechanism of disease, and we speculated that mistrafficking of telomerase complex may occur in HPS. Thus, we studied telomere length and telomerase complex expression in type II alveolar epithelial cells in patients with HPS pulmonary fibrosis (HPSPF) and compared their findings with those in patients with telomere disease (TD), idiopathic pulmonary fibrosis (IPF) and normal controls. Preliminary results with a limited sample size show that telomere length is significantly short in HPSPF. Consistent with these interim results, TERT localization in alveolar type II cells differs in HPSPF compared to TD, IPF and normal lung.

Scientific Focus Area: Genetics and Genomics

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