Two patients with Hermansky Pudlak syndrome type 2 and novel mutations in AP3B1.

Abstract

Hermansky Pudlak syndrome type 2 (HPS2) is a rare disorder associated with mutations in the Adaptor Protein 3 (AP-3) complex, which is involved in sorting transmembrane proteins to lysosomes and related organelles. We now report 2 unrelated subjects with HPS2 who show a characteristic clinical phenotype of oculocutaneous albinism, platelet and T-lymphocyte dysfunction and neutropenia. The subjects were homozygous for different deletions within AP3B1 (g.del180242-180866, c.del153-156), which encodes the AP-3beta3A subunit, resulting in frame shifts and introduction of nonsense substitutions (p.E693fsX13, p.E52fsX11). In the subject with p.E693fsX13, this resulted in expression of a truncated variant beta3A protein. Cytotoxic T-lymphocyte (CTL) clones from both study subjects showed increased cell-surface expression of CD63 and reduced cytotoxicity. Platelets showed impaired aggregation and reduced uptake of (3)H-serotonin. These findings are consistent with CTL granule and platelet dense granule defects, respectively. This report extends the clinical and laboratory description of HPS2.

• Authors: Matt Wenham, Samantha Grieve, Michelle Cummins, Matthew L Jones, Sarah Booth, Rachel Kilner, Philip J Ancliff, Gillian M Griffiths, Andrew D Mumford
• Journal: Haematologica (Haematologica) Vol. 95 Issue 2 Pg. 333-7 (Feb 2010) ISSN: 1592-8721 [Electronic] Italy
• PMID: 19679886 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AP3B1 protein, human
• Adaptor Protein Complex 3
• Adaptor Protein Complex beta Subunits

Topics

• Adaptor Protein Complex 3 (genetics)
• Adaptor Protein Complex beta Subunits (genetics)
• Albinism, Oculocutaneous (genetics)
• Child
• Female
• Hermanski-Pudlak Syndrome (genetics)
• Humans
• Infant
• Male
• Mutation
• Phenotype
• Platelet Function Tests
• T-Lymphocytes, Cytotoxic (metabolism)