Dataset Information

Hermansky-Pudlak syndrome in two African-American brothers.

ABSTRACT: Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, a bleeding disorder, and, in some patients, granulomatous colitis and/or a fatal pulmonary fibrosis. There are eight different subtypes of HPS, each due to mutations in one of eight different genes, whose functions are thought to involve intracellular vesicle formation and trafficking. HPS has been identified in patients of nearly all ethnic groups, though it has primarily been associated with patients of Puerto Rican, Northern European, Japanese and Israeli descent. We report on the diagnosis of HPS type 1 in two African-American patients. Both brothers carried compound heterozygous mutations in HPS1: previously reported p.M325WfsX6 (c.972delC) and a novel silent mutation p.E169E (c.507G > A), which resulted in a splice defect. HPS may be under-diagnosed in African-American patients and other ethnic groups. A history of easy bruising or evidence of a bleeding disorder, combined with some degree of hypopigmentation, should prompt investigation into the diagnosis of HPS.

SUBMITTER: Merideth MA

PROVIDER: S-EPMC2788939 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hermansky-Pudlak syndrome in two African-American brothers.

Merideth Melissa A MA Vincent Lisa M LM Sparks Susan E SE Hess Richard A RA Manoli Irini I O'Brien Kevin J KJ Tsilou Ekaterina E White James G JG Huizing Marjan M Gahl William A WA

American journal of medical genetics. Part A 20090501 5

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, a bleeding disorder, and, in some patients, granulomatous colitis and/or a fatal pulmonary fibrosis. There are eight different subtypes of HPS, each due to mutations in one of eight different genes, whose functions are thought to involve intracellular vesicle formation and trafficking. HPS has been identified in patients of nearly all ethnic groups, though it has primarily been associated ...[more]

PMID: 19334085

Similar Datasets

Project description:RationaleIndividuals with Hermansky-Pudlak syndrome type 1 (HPS-1), an autosomal recessive disorder characterized by defective biogenesis of lysosome-related organelles, develop an accelerated form of progressive fibrotic lung disease. The etiology of pulmonary fibrosis associated with HPS-1 is unknown.ObjectivesTo investigate the potential pathogenesis of pulmonary fibrosis in HPS-1, lung cells and proteins from individuals with HPS-1 were studied.MethodsForty-one subjects with HPS-1 with and without pulmonary fibrosis were evaluated with pulmonary function tests, high-resolution computed tomography scan, and bronchoscopy. Bronchoalveolar lavage cells and analytes were analyzed.Measurements and main resultsConcentrations of total bronchoalveolar lavage cells and alveolar macrophages were significantly higher in epithelial lining fluid from subjects with HPS-1 with and without pulmonary fibrosis compared with healthy research volunteers. Concentrations of cytokines and chemokines (i.e., monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha, and granulocyte-macrophage colony-stimulating factor) in alveolar epithelial lining fluid were significantly higher in subjects with HPS-1 with and without pulmonary fibrosis compared with healthy research volunteers (P < 0.001). In vitro, HPS-1 pulmonary fibrosis alveolar macrophages, which did not express HPS1 mRNA, secreted significantly higher concentrations of monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha, and regulated upon activation, normal T cell expressed and secreted (RANTES) protein compared with normal cells (P = 0.001, P = 0.014, and P = 0.011, respectively). Pirfenidone suppressed HPS-1 alveolar macrophage cytokine and chemokine secretion in vitro in a dose-dependent manner.ConclusionsIn HPS-1, alveolar inflammation predominantly involves macrophages and is associated with high lung concentrations of cytokines and chemokines. HPS-1 alveolar macrophages provide a model system in which to study the pathogenesis and treatment of HPS pulmonary fibrosis.

Dataset Information

Hermansky-Pudlak syndrome in two African-American brothers.

Publications

Hermansky-Pudlak syndrome in two African-American brothers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets