title: 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.affiliation: Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge CB2 0XY, UK.
authors.forename: Matt
authors.initials: M
authors.lastname: Wenham
authors.forename: Samantha
authors.initials: S
authors.lastname: Grieve
authors.forename: Michelle
authors.initials: M
authors.lastname: Cummins
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Jones
authors.forename: Sarah
authors.initials: S
authors.lastname: Booth
authors.forename: Rachel
authors.initials: R
authors.lastname: Kilner
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Ancliff
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Griffiths
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Mumford
mesh_terms: D033963:Adaptor Protein Complex 3 / Q000235:genetics*; D033966:Adaptor Protein Complex beta Subunits / Q000235:genetics*; D016115:Albinism, Oculocutaneous / Q000235:genetics; D002648:Child; D005260:Female; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype; D010979:Platelet Function Tests; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism
chemical_list: C439973:AP3B1 protein, human; D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits
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