DTNBP1 gene

Overview

Gene (OMIM No.)
Function of gene/protein
  • Protein: dystrobrevin binding protein 1
  • A component of the BLOC-1 (biogenesis of lysosomal organelles complex 1) protein complex which regulates the trafficking of proteins in the lysosomal pathway
  • BLOC-1 is required for normal biogenesis of lysosome-related organelles such as melanosomes and platelet dense granules
  • Facilitates the transport of the TYRP1 protein
  • BLOC-1 also plays a role in CNS development and actin cytoskeleton reorganization (from UniProt)
Clinical phenotype
(OMIM phenotype no.)
  • Hermansky-Pudlak syndrome 7 (#614076)
Inheritance
  • Autosomal recessive
Ocular features
Systemic features
  • Skin and hair depigmentation
  • Bleeding diathesis (easy/prolonged bleeding, easy bruising, prolonged/heavy menorrhagia, epistaxis)
  • May be associated with granulomatous colitis
  • Susceptibility to schizophrenia has been reported
Key investigations
  • Orthoptic assessment and refraction
  • OCT to detect foveal hypoplasia
  • Visual evoked potentials to detect evidence of chiasmal misrouting
  • Eye movement recordings
  • Systemic assessment with a pediatrician, haematologists and other relevant specialists
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (albinism)
  • Whole exome sequencing
  • Whole genome sequencing
ManagementOcularSystemic
  • Multidisciplinary approach
Therapies under research
  • None in clinical trials at present
Further information

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References

  1.  Tang TT, Yang F, Chen BS, et al. Dysbindin regulates hippocampal LTP by controlling NMDA receptor surface expression. Proc Natl Acad Sci U S A. 2009;106(50):21395-21400
  2.  Starcevic M, Dell’Angelica EC. Identification of snapin and three novel proteins (BLOS1, BLOS2, and BLOS3/reduced pigmentation) as subunits of biogenesis of lysosome-related organelles complex-1 (BLOC-1). J Biol Chem. 2004;279(27):28393-28401
  3.  Numakawa T, Yagasaki Y, Ishimoto T, et al. Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia. Hum Mol Genet. 2004;13(21):2699-2708
  4.  Li W, Zhang Q, Oiso N, et al. Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1). Nat Genet. 2003;35(1):84-89
  5.  Lowe GC, Sánchez Guiu I, Chapman O, et al. Microsatellite markers as a rapid approach for autozygosity mapping in Hermansky-Pudlak syndrome: identification of the second HPS7 mutation in a patient presenting late in life. Thromb Haemost. 2013;109(4):766-768
  6.  Bryan MM, Tolman NJ, Simon KL, et al. Clinical and molecular phenotyping of a child with Hermansky-Pudlak syndrome-7, an uncommon genetic type of HPS. Mol Genet Metab. 2017;120(4):378-383

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Updated on November 30, 2020
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