Merideth Melissa A, Vincent Lisa M, Sparks Susan E, Hess Richard A, Manoli Irini, O'Brien Kevin J, Tsilou Ekaterina, White James G, Huizing Marjan, Gahl William A
Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-1851, USA.
Am J Med Genet A. 2009 May;149A(5):987-92. doi: 10.1002/ajmg.a.32757.
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.
赫尔曼斯基-普德拉克综合征(HPS)是一种常染色体隐性疾病,其特征为眼皮肤白化病、出血性疾病,部分患者还伴有肉芽肿性结肠炎和/或致命性肺纤维化。HPS有八种不同的亚型,每种亚型由八个不同基因中的一个发生突变所致,这些基因的功能被认为与细胞内囊泡的形成和运输有关。几乎在所有种族的患者中都发现了HPS,不过它主要与波多黎各、北欧、日本和以色列血统的患者有关。我们报告了两名非裔美国患者1型HPS的诊断情况。两兄弟在HPS1基因中携带复合杂合突变:先前报道的p.M325WfsX6(c.972delC)和一个新的沉默突变p.E169E(c.507G>A),该突变导致了剪接缺陷。在非裔美国患者和其他种族群体中,HPS可能未得到充分诊断。有易瘀伤病史或出血性疾病证据,再加上一定程度的色素减退,应促使对HPS的诊断进行调查。