FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 338:1258-1265 April 30, 1998 Number 18 Next

	Full Text PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Hermansky–Pudlak syndrome is characterized by oculocutaneous albinism, a storage-pool deficiency, and lysosomal accumulation of ceroid lipofuscin, which causes pulmonary fibrosis and granulomatous colitis in some cases. All identified affected patients in northwest Puerto Rico are homozygous for a 16-bp duplication in exon 15 of a recently cloned gene, HPS. We compared the clinical and laboratory characteristics of these patients with those of patients without the 16-bp duplication.

Methods Forty-nine patients — 27 Puerto Ricans and 22 patients from the mainland United States who were not of Puerto Rican descent — were given a diagnosis on the basis of albinism and the absence of platelet dense bodies. We used the polymerase chain reaction to determine which patients carried the 16-bp duplication.

Results Twenty-five of the Puerto Rican patients were homozygous for the 16-bp duplication, whereas none of the non–Puerto Rican patients carried this mutation. Like the patients without the duplication, the patients with the 16-bp duplication had a broad variation in pigmentation. Nine of 16 adults with the duplication, but none of the 10 without it, had a diffusing capacity for carbon monoxide that was less than 80 percent of the predicted value. High-resolution computed tomography in 12 patients with the 16-bp duplication revealed minimal fibrosis in 8, moderate fibrosis in 1, severe fibrosis in 1, and no fibrosis in 2. Computed tomography in eight patients without the duplication revealed minimal fibrosis in three and no fibrosis in the rest. Inflammatory bowel disease developed in eight patients (four in each group) between 3 and 25 years of age.

Conclusions The 16-bp duplication in exon 15 of HPS, which we found only in Puerto Rican patients, is associated with a broad range of pigmentation and an increased risk of restrictive lung disease in adults.

Source Information

From the Heritable Disorders Branch (W.A.G., S.H., V.S., I.B.) and the Biometry and Mathematical Statistics Branch (J.T.), National Institute of Child Health and Human Development; the Pulmonary–Critical Care Medicine Branch, National Heart, Lung, and Blood Institute (M.B.); the Ophthalmic Genetics and Clinical Services Branch, National Eye Institute (M.I.K.-K., F.I., E.M.K.); and the Howard Hughes Medical Institute, National Institutes of Health Research Scholars Program (S.H.) — all in Bethesda, Md.; and Gastroenterology Associates of Northern Virginia, Fairfax (L.F.D.).

Address reprint requests to Dr. Gahl at the Section on Human Biochemical Genetics, 10 Center Dr., MSC 1830, Bldg. 10, Rm. 9S-241, NICHD, NIH, Bethesda, MD 20892-1830.

Full Text of this Article

This article has been cited by other articles:

• Rouhani, F. N., Brantly, M. L., Markello, T. C., Helip-Wooley, A., O'Brien, K., Hess, R., Huizing, M., Gahl, W. A., Gochuico, B. R. (2009). Alveolar Macrophage Dysregulation in Hermansky-Pudlak Syndrome Type 1. Am. J. Respir. Crit. Care Med. 180: 1114-1121 [Abstract] [Full Text]  
• Tager, A. M., Sharma, A., Mark, E. J. (2009). Case 32-2009 -- A 27-Year-Old Man with Progressive Dyspnea. NEJM 361: 1585-1593 [Full Text]  
• King, S. M., McNamee, R. A., Houng, A. K., Patel, R., Brands, M., Reed, G. L. (2009). Platelet Dense-Granule Secretion Plays a Critical Role in Thrombosis and Subsequent Vascular Remodeling in Atherosclerotic Mice. Circulation 120: 785-791 [Abstract] [Full Text]  
• Young, L. R., Pasula, R., Gulleman, P. M., Deutsch, G. H., McCormack, F. X. (2007). Susceptibility of Hermansky-Pudlak Mice to Bleomycin-Induced Type II Cell Apoptosis and Fibrosis. Am. J. Respir. Cell Mol. Bio. 37: 67-74 [Abstract] [Full Text]  
• Ren, P., Rosas, I. O., MacDonald, S. D., Wu, H.-P., Billings, E. M., Gochuico, B. R. (2007). Impairment of Alveolar Macrophage Transcription in Idiopathic Pulmonary Fibrosis. Am. J. Respir. Crit. Care Med. 175: 1151-1157 [Abstract] [Full Text]  
• Bahadori, R., Rinner, O., Schonthaler, H. B., Biehlmaier, O., Makhankov, Y. V., Rao, P., Jagadeeswaran, P., Neuhauss, S. C. F. (2006). The Zebrafish fade out Mutant: A Novel Genetic Model for Hermansky-Pudlak Syndrome.. IOVS 47: 4523-4531 [Abstract] [Full Text]  
• Zhou, M., Gradstein, L., Gonzales, J. A., Tsilou, E. T., Gahl, W. A., Chan, C.-C. (2006). Ocular Pathologic Features of Hermansky-Pudlak Syndrome Type 1 in an Adult. Arch Ophthalmol 124: 1048-1051 [Full Text]  
• Young, L. R., Borchers, M. T., Allen, H. L., Gibbons, R. S., McCormack, F. X. (2006). Lung-Restricted Macrophage Activation in the Pearl Mouse Model of Hermansky-Pudlak Syndrome. J. Immunol. 176: 4361-4368 [Abstract] [Full Text]  
• Pulipparacharuvil, S., Akbar, M. A., Ray, S., Sevrioukov, E. A., Haberman, A. S., Rohrer, J., Kramer, H. (2005). Drosophila Vps16A is required for trafficking to lysosomes and biogenesis of pigment granules. J. Cell Sci. 118: 3663-3673 [Abstract] [Full Text]  
• Boissy, R. E., Richmond, B., Huizing, M., Helip-Wooley, A., Zhao, Y., Koshoffer, A., Gahl, W. A. (2005). Melanocyte-Specific Proteins Are Aberrantly Trafficked in Melanocytes of Hermansky-Pudlak Syndrome-Type 3. Am. J. Pathol. 166: 231-240 [Abstract] [Full Text]  
• Gwynn, B., Martina, J. A., Bonifacino, J. S., Sviderskaya, E. V., Lamoreux, M. L., Bennett, D. C., Moriyama, K., Huizing, M., Helip-Wooley, A., Gahl, W. A., Webb, L. S., Lambert, A. J., Peters, L. L. (2004). Reduced pigmentation (rp), a mouse model of Hermansky-Pudlak syndrome, encodes a novel component of the BLOC-1 complex. Blood 104: 3181-3189 [Abstract] [Full Text]  
• Poddar, R. K., Coley, S., Pavord, S. (2004). Hermansky-Pudlak syndrome in a pregnant patient. Br J Anaesth 93: 740-742 [Abstract] [Full Text]  
• Ciciotte, S. L., Gwynn, B., Moriyama, K., Huizing, M., Gahl, W. A., Bonifacino, J. S., Peters, L. L. (2003). Cappuccino, a mouse model of Hermansky-Pudlak syndrome, encodes a novel protein that is part of the pallidin-muted complex (BLOC-1). Blood 101: 4402-4407 [Abstract] [Full Text]  
• Avila, N. A., Brantly, M., Premkumar, A., Huizing, M., Dwyer, A., Gahl, W. A. (2002). Hermansky-Pudlak Syndrome: Radiography and CT of the Chest Compared with Pulmonary Function Tests and Genetic Studies. Am. J. Roentgenol. 179: 887-892 [Abstract] [Full Text]  
• Novak, E. K., Gautam, R., Reddington, M., Collinson, L. M., Copeland, N. G., Jenkins, N. A., McGarry, M. P., Swank, R. T. (2002). The regulation of platelet-dense granules by Rab27a in the ashen mouse, a model of Hermansky-Pudlak and Griscelli syndromes, is granule-specific and dependent on genetic background. Blood 100: 128-135 [Abstract] [Full Text]  
• Harrison, C, Khair, K, Baxter, B, Russell-Eggitt, I, Hann, I, Liesner, R (2002). Hermansky-Pudlak syndrome: infrequent bleeding and first report of Turkish and Pakistani kindreds. Arch. Dis. Child. 86: 297-301 [Abstract] [Full Text]  
• Saif, M W, Hamilton, J M (2001). A 25 year old woman presenting with bleeding disorder and nystagmus. Postgrad. Med. J. 77: e6-6 [Full Text]  
• Huizing, M., Sarangarajan, R., Strovel, E., Zhao, Y., Gahl, W. A., Boissy, R. E. (2001). AP-3 Mediates Tyrosinase but Not TRP-1 Trafficking in Human Melanocytes. Mol. Biol. Cell 12: 2075-2085 [Abstract] [Full Text]  
• Gwynn, B., Ciciotte, S. L., Hunter, S. J., Washburn, L. L., Smith, R. S., Andersen, S. G., Swank, R. T., Dell'Angelica, E. C., Bonifacino, J. S., Eicher, E. M., Peters, L. L. (2000). Defects in the cappuccino (cno) gene on mouse chromosome 5 and human 4p cause Hermansky-Pudlak syndrome by an AP-3-independent mechanism. Blood 96: 4227-4235 [Abstract] [Full Text]  
• Brantly, M., Avila, N. A., Shotelersuk, V., Lucero, C., Huizing, M., Gahl, W. A. (2000). Pulmonary Function and High-Resolution CT Findings in Patients With an Inherited Form of Pulmonary Fibrosis, Hermansky-Pudlak Syndrome, Due to Mutations in HPS-1*. Chest 117: 129-136 [Abstract] [Full Text]  
• Toro, J., Turner, M., Gahl, W. A. (1999). Dermatologic Manifestations of Hermansky-Pudlak Syndrome in Patients With and Without a 16-Base Pair Duplication in the HPS1 Gene. Arch Dermatol 135: 774-780 [Abstract] [Full Text]