Skip to main content
. 2020 Nov 5;106(2):337–350. doi: 10.3324/haematol.2020.248153

Figure 4.

Figure 4.

Hermansky-Pudlak syndrome. Syndromic platelet defect resulting from the abnormal biogenesis of dense granules with an autosomal recessive inheritance. (A) Summarizes the genotype/phenotype relationship of different types of Hermansky-Pudlak syndrome (HPS) regrouped according to the four multi-protein complexes involved in different steps of lysosome-related organelle (LRO) biogenesis including vesicle formation and/or trafficking: BLOC1, 2 and 3 and AP-3 with each containing several subunits. Variants in HPS 7, 8 and 9 are causal in BLOC1 but with mild clinical consequences. For BLOC2, variants in HPS 3, 5 or 6 give syndromes of moderate severity; they are rare but a variant of HPS 3 occurs in Puerto Rican communities. The most frequent causes of HPS are BLOC3 defects (variants in HPS 1 or 4). The syndromes are severe and are associated with lung fibrosis and gastro-intestinal defects; in Puerto Rico a community is affected by a common HPS1 variant. In the last group, defects of AP-3 are associated with neutropenia and infections. (B) A scheme illustrates the major steps of granule biogenesis. Dense granules may derive from the endolysosomal system, including either early or late endosomes. As secretory granules the membrane constituents including membrane transporters come from the Golgi complex. A network of interconnected and functionally distinct tubular subdomains transports their cargoes along microtubule tracks from the endosomes. Tubules ferry contents from the trans-Golgi-network and the plasma membrane to the LRO, a system that requires the coordination of numerous effectors. Components stored in dense granules or associated with their membranes are shown. (C) Platelets from a control and a patient with HPS3 examined by electron microscopy as whole mounts are shown. The dense granules observed in controls as black spots are absent from the patient’s platelet. AP-3: adaptor protein-3; BLOC: biogenesis of lysosome-related organelles complex; LRO: lysosome-related organelle; OCA: oculocutaneous albinism; MVB: multivesicular body.