Journal des syndromes génétiques et de la thérapie génique
Libre accès
ISSN: ISSN: 2157-7412
ISSN: ISSN: 2157-7412
van der Vis JJ, ten Klooster L, van Oosterhout MFM, Grutters JC and van Moorsel CHM
Hermansky-Pudlak syndrome (HPS) is an autosomal recessive multisystem disease characterized by bleeding disorders and oculocutaneous albinism. In some patients the syndrome is accompanied by granulomatous colitis, immunodeficiency or pulmonary fibrosis. To date nine genes are associated with the syndrome, resulting in subtypes HPS-1 to HPS-9. Pulmonary fibrosis is most commonly associated with HPS-1. The clinical course of patients with HPS and pulmonary fibrosis resembles that of idiopathic pulmonary fibrosis (IPF). Our aim was to establish the prevalence of HPS in a cohort of IPF patients.
Methods: 127 patients diagnosed with IPF based on the criteria set by the ATS/ERS/JRS/ALAT were retrospectively screened for clinical features of HPS. Genetic analysis was performed in patients with pulmonary fibrosis and 2 or more clinical features of HPS. Genomic DNA was extracted from peripheral blood of each individual using standard method. The coding exons and the exon-intron boundaries of HPS1 gene were amplified and sequenced.
Results: Out of 127 IPF patients, 22 patients had 1 feature and 4 patients had ≥ 2 features of HPS. These 4 patients were genetically analyzed. Genetic analysis identified one compound heterozygous patient with 2 mutations in exon 13, Q397SfsX1 and R439X. Both mutations were not present in our IPF cohort and healthy controls. In the other 3 IPF patients no mutations were found.
Conclusion: Out of 127 IPF patients we identified one compound heterozygous patient with 2 mutations in the HPS1 gene. HPS is a very rare syndrome, but recognizing is important because of the clinical consequences, particularly when the patient is referred for lung transplantation. Therefore, pulmonologists should be aware of HPS as an underlying cause of pulmonary fibrosis.