HPS1 gene

Overview
Albinism
Additional information
References

Overview

Gene (OMIM No.)	HPS1 (#604982)
Function of gene/protein	Protein: biogenesis of lysosomal organelles complex 3 subunit 1 A component of the biogenesis of lysosome-related organelles complex-3 (BLOC-3) complex along with HPS4 BLOC-3 complex plays a role in the biogenesis of lysosomes and lysosome-related organelles (LROs) such as melanosomes and platelet dense granules Lysosomes are cytoplasmic organelles that serve as a major degradative compartment in eukaryotes LROs have similar features to lysosomes but have distinct morphology, composition and/or function
Clinical phenotype (OMIM phenotype no.)	Hermansky-Pudlak syndrome 1 (#203300)
Inheritance	Autosomal recessive
Ocular features	Albinism Intra- and interfamilial variability in disease severity
Systemic features	Skin and hair depigmentation Bleeding diathesis (easy/prolonged bleeding, easy bruising, prolonged/heavy menorrhagia, epistaxis) At risk of developing pulmonary fibrosis (onset usually during early 30s) and granulomatous colitis
Key investigations	Orthoptic assessment and refraction OCT to detect foveal hypoplasia Visual evoked potentials to detect evidence of chiasmal misrouting Eye movement recordings Systemic assessment with a pediatrician, haematologists and other relevant specialists
Molecular diagnosis	Next generation sequencing Targeted gene panels (albinism) Whole exome sequencing Whole genome sequencing
Management	Ocular Management of albinism Systemic Multidisciplinary approach
Therapies under research	A phase 2 randomised controlled trial of oral pirfenidone (an antifibrotic drug) for HPS1 and *HPS4* associated pulmonary fibrosis showed equivocal results between placebo and intervention arms Extended treatment of three patients with HPS1 mutations demonstrated potential clinical benefit
Further information	Medline Plus

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Additional information

Hermansky-Pudlak syndrome (HPS) patients with BLOC-3 defects (HPS1 or HPS4) have more severe ocular and systemic phenotypes compared to those with BLOC-2 defects (HPS3, HPS5 and HPS6).^[2] HPS is very common among Puerto Ricans, especially in the north-western part of the country with an incidence of roughly 1:1,800.^[3] All HPS patients from this part of the country are homozygous for the 16-base pair (bp) duplication in exon 15 of the HPS1 gene due to a founder mutation.^[3-5]

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References

Kornfeld S, Mellman I. The biogenesis of lysosomes. Annu Rev Cell Biol. 1989;5:483-525
Huizing M, Helip-Wooley A, Westbroek W, Gunay-Aygun M, Gahl WA. Disorders of lysosome-related organelle biogenesis: clinical and molecular genetics. Annu Rev Genomics Hum Genet. 2008;9:359-386
Santiago Borrero PJ, Rodríguez-Pérez Y, Renta JY, et al. Genetic testing for oculocutaneous albinism type 1 and 2 and Hermansky-Pudlak syndrome type 1 and 3 mutations in Puerto Rico. J Invest Dermatol. 2006;126(1):85-90
Gahl WA, Brantly M, Kaiser-Kupfer MI, et al. Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome). N Engl J Med. 1998;338(18):1258-1264
Toro J, Turner M, Gahl WA. Dermatologic manifestations of Hermansky-Pudlak syndrome in patients with and without a 16-base pair duplication in the HPS1 gene. Arch Dermatol. 1999;135(7):774-780
Carmona-Rivera C, Simeonov DR, Cardillo ND, Gahl WA, Cadilla CL. A divalent interaction between HPS1 and HPS4 is required for the formation of the biogenesis of lysosome-related organelle complex-3 (BLOC-3). Biochim Biophys Acta. 2013;1833(3):468-478
Ito S, Suzuki T, Inagaki K, et al. High frequency of Hermansky-Pudlak syndrome type 1 (HPS1) among Japanese albinism patients and functional analysis of HPS1 mutant protein. J Invest Dermatol. 2005;125(4):715-720

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Updated on November 30, 2020

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