Hermansky-Pudlak syndrome (HPS) is a set of rare disorders characterized by oculocutaneous albinism (reduced or absent melanin pigment in the skin, hair and eyes), bleeding disorders, pulmonary fibrosis, immunodeficiency and inflammatory bowel disease (IBD).
The disorders result from mutations in 11 different genes that are responsible for the biogenesis and trafficking of lysosome-related organelles involved in pigmentation, blood clotting and immunity, among other functions.
One rare subtype, HPS-7, is associated with mutations in the dysbindin gene, DTNBP1. The molecular function of this gene is unknown.
Janet Markle, PhD, and colleagues describe a 15-month-old boy with HPS-7 who had a novel splicing mutation in DTNBP1 and presented with very early onset IBD. He showed elevated expression of genes involved in the JAK/STAT signaling and immune cell activation pathways.
This case, reported in the European Journal of Medical Genetics, underscores the emerging immunological consequences of dysbindin deficiency, and suggests that DTNBP1 mutations may underlie some rare cases of very early onset IBD.
The paper’s co-first authors were Sagar Bhattad, MD, a specialist in pediatric immunology and rheumatology from Bangalore, India, and Vanderbilt medical student Michael Libre. Joseph Choi, a graduate student in the Markle lab at Vanderbilt, also contributed to the paper.
The study was supported in part by National Institutes of Health grants DK058404 and CA236733.
