Hermansky–Pudlak syndrome type 1 in patients of Indian descent
Introduction
Hermansky–Pudlak syndrome (HPS; MIM #203300) is an autosomal recessive disorder characterized by oculocutaneous albinism and a bleeding diathesis; some patients exhibit lysosomal accumulation of ceroid lipofuscin, granulomatous colitis, or pulmonary fibrosis that is fatal in the fourth or fifth decade [1], [2], [3], [4], [5]. Genetic heterogeneity is supported by the existence of at least 15 HPS mouse models [6], and mutations in eight different genes have been identified in humans with HPS [7], [8]. The HPS genes with known function have roles in the biogenesis and/or function of intracellular organelles required in membrane and protein trafficking [8]. The genetic heterogeneity of HPS gives rise to clinical heterogeneity. For example, only patients with mutations in HPS1 or HPS4 develop pulmonary fibrosis [8], [9], [10].
HPS is a rare disorder that has been identified in patients worldwide, including Puerto Rico, Japan, Northern Europe, and Israel [3], [7], [8], [11], [12], [13], [14], [15]. In addition, HPS-1, the most common HPS subtype, was recently reported in two African American siblings [16]. HPS-1 results from mutations in the HPS1 gene located on 10q23.1–q23.3 [17] and occurs largely as a genetic isolate in individuals from northwest Puerto Rico [11]. Among non-Puerto Ricans, HPS-1 accounts for ∼50% of all HPS cases [7], [18]. Here, we report the first diagnosis of HPS in patients of Indian descent arising from two different mutations in HPS1.
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Patients and cells
Written, informed consent was obtained for enrollment in a protocol approved by the National Human Genome Research Institute (NHGRI) institutional review board to evaluate the clinical and molecular aspects of HPS. Patient numbers conformed to a master list of NIH subjects with HPS. The diagnosis was based upon the absence of platelet dense bodies on whole-mount electron microscopy and the presence of hypopigmentation, decreased visual acuity, and nystagmus. Primary skin fibroblast and
Case reports
Patient HPS152 was a female adopted from Hyderbad, India at 14 months of age, and was 8 years old at the time of our initial evaluation. At the time of adoption, an ophthalmologist diagnosed oculocutaneous albinism (Fig. 1A–C). Frequent bruising and epistaxis occurred, with bleeding for up to 1 h. These findings and the absence of platelet dense bodies on electron microscopy (Fig. 1D) led to the diagnosis of HPS at age 7. No transfusions, DDAVP (1-deamino-8-d-arginine vasopressin), or cautery were
Discussion
Our mutation analysis of unclassified patients with Hermansky–Pudlak syndrome revealed three apparently unrelated patients from different regions of India with mutations in the HPS1 gene. All three patients displayed iris transillumination, pale fundi, hypopigmentation, nystagmus, decreased visual acuity, and absence of platelet dense bodies. None of the patients had developed pulmonary fibrosis or a decrease of pulmonary function at the time of evaluation, likely because all three patients
Acknowledgments
Isa Bernardini, Roxanne Fischer, Heidi Dorward, and Wendy Westbroek provided excellent technical assistance. This work was supported by the Intramural Research programs of the National Human Genome Research Institute and National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
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A cross-sectional examination of visual acuity by specific type of albinism
2016, Journal of AAPOSCitation Excerpt :Reports of patients with HPS are abundant, but many do not include BCVA. Reports of visual acuity in HPS are shown in Table 5.21,32,45-47 In our study, the 22 patients with HPS had binocular BCVA ranging from 20/50 to 20/300.
Clinical, molecular, and cellular features of non-puerto rican hermansky-pudlak syndrome patients of hispanic descent
2011, Journal of Investigative DermatologyCitation Excerpt :So far, only two BLOC-1 patients have been reported, one HPS-7 patient () and one HPS-8 family (); however, no detailed clinical features have been provided apart from hypopigmentation, silvery hair (in HPS-8), and a bleeding diathesis. HPS has been described in patients worldwide (Witkop et al., 1990; Brantly et al., 2000; Huizing et al., 2001; Anderson et al., 2003; Ito et al., 2005; Merideth et al., 2009; Vincent et al., 2009) but is common on the island of Puerto Rico. One in 1,800 Puerto Ricans in the northwest part of the island suffers from HPS type 1 (HPS-1; Witkop et al., 1990) because of a 16 bp duplication in exon 15 of the HPS1 gene (Oh et al., 1996).
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