Two patients with Hermansky Pudlak syndrome type 2 and novel mutations in AP3B1.
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.
Wenham
Matt
M
Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge CB2 0XY, UK.
Grieve
Samantha
S
Cummins
Michelle
M
Jones
Matthew L
ML
Booth
Sarah
S
Kilner
Rachel
R
Ancliff
Philip J
PJ
Griffiths
Gillian M
GM
Mumford
Andrew D
AD
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
C439973:AP3B1 protein, human; D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits
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