HPS1

The HPS1 gene provides instructions for making a protein that forms part of a complex called biogenesis of lysosome-related organelles complex-3 (BLOC-3). Although the specific function of BLOC-3 is not well understood, it plays a role in the formation and movement (trafficking) of a group of cellular structures called lysosome-related organelles (LROs). LROs are very similar to compartments within the cell called lysosomes, which digest and recycle materials. However, LROs perform specialized functions and are found only in certain cell types.

Within pigment cells (melanocytes), LROs called melanosomes produce and distribute melanin, which is the substance that gives skin, hair, and eyes their color. A different type of LRO is found in platelets, the blood cells involved in normal blood clotting. These LROs, called dense granules, release chemical signals that cause platelets to stick together and form a blood clot. LROs are also found in other specialized cells, including certain cells of the lungs.

Hermansky-Pudlak syndrome - caused by mutations in the HPS1 gene

At least 27 mutations in the HPS1 gene have been found to cause Hermansky-Pudlak syndrome type 1. These mutations impair the normal function of BLOC-3, disrupting the size, structure, and function of LROs in cells throughout the body. The most common mutation causes a duplication of genetic material within the HPS1 gene and is found in people from northwest Puerto Rico. Specifically, this mutation results in an extra 16 DNA building blocks (nucleotides) within the gene (written as 1470_1468dup16).

People with Hermansky-Pudlak syndrome have abnormally light coloring of the skin, hair, and eyes because melanosomes do not distribute melanin properly. The absence of dense granules within platelets leads to bleeding problems in affected individuals. A severe lung disease called pulmonary fibrosis may also develop due to abnormal LROs in certain lung cells.