Cellular, molecular and clinical characterization of patients with Hermansky-Pudlak syndrome type 5

Marjan Huizing, Richard Hess, Heidi Dorward, David A. Claassen, Amanda Helip-Wooley, Robert Kleta, Muriel I. Kaiser-Kupfer, James G. White, William A. Gahl

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Hermansky-Pudlak syndrome (HPS) is a disorder of lysosome-related organelles such as melanosomes and platelet dense granules. Seven genes are now associated with HPS in humans. An accurate diagnosis of each HPS subtype has important prognostic and treatment implications. Here we describe the cellular, molecular, and clinical aspects of the recently identified HPS-5 subtype. We first analyzed the genomic organization and the RNA expression pattern of HPS5, located on chromosome 11p14, and demonstrated tissue-specific expression of at least three alternatively spliced HPS5 mRNA transcripts, coding for HPS5A and HPS5B proteins, that differ at their 5'-ends. Genetic screening of 15 unassigned HPS patients yielded six new HPS5 mutations in four patients. Clinically, our HPS-5 patients exhibited iris transillumination, variable hair and skin pigmentation, and absent platelet dense bodies, but not pulmonary fibrosis or granulomatous colitis. In two patients with homozygous missense mutations, hemizygosity was ruled out by gene-dosage multiplex polymerase chain reaction, and immunocytochemical analyses of their fibroblasts supported the HPS-5 diagnosis. Specifically, LAMP-3 distribution was restricted to the perinuclear region in HPS-5 fibroblasts, in contrast to the normal LAMP-3 distribution, which extended to the periphery. This specific intracellular vesicle distribution in fibroblasts, in combination with the clinical features, will improve the characterization of the HPS-5 subtype.

Original languageEnglish (US)
Pages (from-to)711-722
Number of pages12
JournalTraffic
Volume5
Issue number9
DOIs
StatePublished - Sep 2004

Fingerprint

Hermanski-Pudlak Syndrome
Fibroblasts
Platelets
Genes
Transillumination
Polymerase chain reaction
Chromosomes
Skin
Screening
RNA
Tissue
Messenger RNA
Blood Platelets
Skin Pigmentation
Melanosomes
Proteins
Gene Dosage
Pulmonary Fibrosis
Multiplex Polymerase Chain Reaction
Genetic Testing

Keywords

  • Gene-dosage polymerase chain reaction (PCR)
  • Hermansky-Pudlak syndrome (HPS)
  • Lysosome-related organelle
  • Melanosome
  • Organelle biogenesis
  • Platelet dense granule

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Structural Biology
  • Molecular Biology
  • Genetics

Cite this

Huizing, M., Hess, R., Dorward, H., Claassen, D. A., Helip-Wooley, A., Kleta, R., ... Gahl, W. A. (2004). Cellular, molecular and clinical characterization of patients with Hermansky-Pudlak syndrome type 5. Traffic, 5(9), 711-722. https://doi.org/10.1111/j.1600-0854.2004.00208.x

Cellular, molecular and clinical characterization of patients with Hermansky-Pudlak syndrome type 5. / Huizing, Marjan; Hess, Richard; Dorward, Heidi; Claassen, David A.; Helip-Wooley, Amanda; Kleta, Robert; Kaiser-Kupfer, Muriel I.; White, James G.; Gahl, William A.

In: Traffic, Vol. 5, No. 9, 09.2004, p. 711-722.

Research output: Contribution to journalArticle

Huizing, M, Hess, R, Dorward, H, Claassen, DA, Helip-Wooley, A, Kleta, R, Kaiser-Kupfer, MI, White, JG & Gahl, WA 2004, 'Cellular, molecular and clinical characterization of patients with Hermansky-Pudlak syndrome type 5', Traffic, vol. 5, no. 9, pp. 711-722. https://doi.org/10.1111/j.1600-0854.2004.00208.x
Huizing, Marjan ; Hess, Richard ; Dorward, Heidi ; Claassen, David A. ; Helip-Wooley, Amanda ; Kleta, Robert ; Kaiser-Kupfer, Muriel I. ; White, James G. ; Gahl, William A. / Cellular, molecular and clinical characterization of patients with Hermansky-Pudlak syndrome type 5. In: Traffic. 2004 ; Vol. 5, No. 9. pp. 711-722.
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