A BLOC-1 mutation screen reveals a novel BLOC1S3 mutation in Hermansky–Pudlak Syndrome type 8
Version of Record online: 2 AUG 2012
Published 2012. This article is a US Government work and is in the public domain in the USA.
Pigment Cell & Melanoma Research
Volume 25, Issue 5, pages 584–591, September 2012
How to Cite
Cullinane, A. R., Curry, J. A., Golas, G., Pan, J., Carmona-Rivera, C., Hess, R. A., White, J. G., Huizing, M. and Gahl, W. A. (2012), A BLOC-1 mutation screen reveals a novel BLOC1S3 mutation in Hermansky–Pudlak Syndrome type 8. Pigment Cell & Melanoma Research, 25: 584–591. doi: 10.1111/j.1755-148X.2012.01029.x
- Issue online: 28 AUG 2012
- Version of Record online: 2 AUG 2012
- Accepted manuscript online: 18 JUN 2012 12:12PM EST
- PUBLICATION DATA Received 15 February 2012, revised and accepted for publication 11 June 2012, published online 18 June 2012
- Hermansky–Pudlak Syndrome;
Hermansky–Pudlak 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 1–6. 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 patient’s 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.