Molecular Genetics of Hermansky–Pudlak Syndrome

Abstract

Hermansky–Pudlak syndrome (HPS) is an autosomal recessive, genetically heterogeneous disorder characterised by oculocutaneous albinism and a bleeding diathesis. Subtype specific features such as neutropenic immunodeficiency and fatal lung fibrosis also occur. To date, nine human HPS subtypes (HPS‐1 to HPS‐9) and their associated genes have been identified. All of the HPS protein products are involved in biogenesis of lysosome‐related organelles (LROs) in specialised cells, including melanosomes in melanocytes and delta granules in platelets. The HPS proteins are all components of one of three biogenesis of lysosome‐related organelles complexes (BLOC‐1, BLOC‐2 or BLOC‐3) or the adaptor protein complex‐3. These complexes are essential for the correct formation of LROs, which are produced by the complex interaction of proteins, membranes and vesicles from the endocytic and biosynthetic pathways. Cells from patients with LRO disorders serve as useful tools for elucidating the complex pathways involved in the biogenesis of these organelles. Key Concepts: HPS is caused by mutations in nine known genes and is characterised by oculocutaneous albinism and a bleeding tendency. The proteins that are encoded by the HPS genes are all required for the correct formation of lysosome‐related organelles (LROs). LROs share features with lysosomes but have distinct morphology, composition and/or functions. LROs are maintained by the regulated flow of proteins, membranes and vesicles among the complex endosomal machinery. Novel players of LRO biogenesis are revealed by human disease and animal mutations, which continue to provide invaluable resources for elucidating the complex pathways involved in the biogenesis of these organelles.

Primary Hemostasis Disorders as a Cause of Heavy Menstrual Bleeding in Women of Reproductive Age

“…Bleeding manifestations of HPS also vary and include excessive bruising, epistaxis, gingival bleeding, or other forms of mucosal bleeding, surgical or dental bleeding, menorrhagia and postpartum hemorrhage. Restrictive lung disease typically becomes clinically apparent in the early 30s and granulomatous colitis is severe in about 15% of affected individuals [10,57].…”