A BLOC-1 mutation screen reveals a novel BLOC1S3 mutation in Hermansky-Pudlak Syndrome type 8

作者：Cullinane Andrew R^*; Curry James A; Golas Gretchen; Pan James; Carmona Rivera Carmelo; Hess Richard A; White James G; Huizing Marjan; Gahl William A

来源：Pigment Cell & Melanoma Research, 2012, 25(5): 584-591.

DOI：10.1111/j.1755-148X.2012.01029.x

• Hermansky-Pudlak Syndrome
• BLOC-1
• HPS-8
• BLOC1S3

HermanskyPudlak Syndrome (HPS) is a genetically heterogeneous disorder of lysosome-related organelle biogenesis and is characterized by oculocutaneous albinism and a bleeding diathesis. Over the past decade, we screened 250 patients with HPS-like symptoms for mutations in the genes responsible for HPS subtypes 16. We identified 38 individuals with no functional mutations, and therefore, we analyzed all eight genes encoding the biogenesis of lysosome-related organelles complex-1 (BLOC-1) proteins in these individuals. Here, we describe the identification of a novel nonsense mutation in BLOC1S3 (HPS-8) in a 6-yr-old Iranian boy. This mutation caused nonsense-mediated decay of BLOC1S3 mRNA and destabilized the BLOC-1 complex. Our patients melanocytes showed aberrant localization of TYRP1, with increased plasma membrane trafficking. These findings confirm a common cellular defect for HPS patients with defects in BLOC-1 subunits. We identified only two patients with BLOC-1 defects in our cohort, suggesting that other HPS genes remain to be identified.

• 出版日期2012-9