title: Clinical and molecular phenotyping of a child with Hermansky-Pudlak syndrome-7, an uncommon genetic type of HPS.
abstract: Hermansky-Pudlak syndrome (HPS) is a rare inherited disorder with ten reported genetic types; each type has defects in subunits of either Adaptor Protein-3 complex or Biogenesis of Lysosome-related Organelles Complex (BLOC)-1, -2, or -3. Very few patients with BLOC-1 deficiency (HPS-7, -8, and -9 types) have been diagnosed. We report results of comprehensive clinical testing and molecular analyses of primary fibroblasts from a new case of HPS-7.
  
  
  
  A 6-year old Paraguayan male presented with hypopigmentation, ocular albinism, nystagmus, reduced visual acuity, and easy bruising. He also experienced delayed motor and language development as a very young child; head and chest trauma resulted in intracranial hemorrhage with subsequent right hemiparesis and lung scarring. There was no clinical evidence of immunodeficiency or colitis. Whole mount transmission electron microscopy revealed absent platelet delta granules; platelet aggregation testing was abnormal. Exome sequencing revealed a homozygous nonsense mutation in the Dystrobrevin binding protein 1 (DTNBP1) gene [NM_032122.4: c.307C>T; p.Gln103*], previously reported in a Portuguese adult. The gene encodes the dysbindin subunit of BLOC-1. Dysbindin protein expression was negligible in our patient's dermal fibroblasts, while his DTNBP1 mRNA level was similar to that of a normal control.
  
  
  
  Comprehensive clinical evaluation of the first pediatric case reported with HPS-7 reveals oculocutaneous albinism and platelet storage pool deficiency; his phenotype is consistent with findings in other patients with BLOC-1 disorders. This patient's markedly reduced Dysbindin protein expression in HPS-7 resulted from a mechanism other than nonsense mediated decay.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Melanie M
authors.initials: MM
authors.lastname: Bryan
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Nathanial J
authors.initials: NJ
authors.lastname: Tolman
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Simon
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Marjan
authors.initials: M
authors.lastname: Huizing
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Hufnagel
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Brooks
authors.affiliation: National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Speransky
authors.affiliation: NIH Intramural Sequencing Center, National Institutes of Health, 5625 Fishers Lane, Rockville, MD 20852, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Mullikin
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA; Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, 9000 Rockville Pike, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.affiliation: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, 9000 Rockville Pike, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: maychristine.malicdan@nih.gov.
authors.forename: May Christine V
authors.initials: MCV
authors.lastname: Malicdan
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Bernadette R
authors.initials: BR
authors.lastname: Gochuico
mesh_terms: D002648:Child; D018389:Codon, Nonsense; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D059472:Exome; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D017422:Sequence Analysis, DNA
chemical_list: D018389:Codon, Nonsense; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins
keywords: Biogenesis of Lysosome-related Organelles Complex-1; DTNBP1; Dysbindin; Oculocutaneous albinism; Platelet storage pool disorder