Hämostaseologie, Inhaltsverzeichnis

Hamostaseologie 2014; 34(04): 301-309
DOI: 10.5482/HAMO-14-06-0024

Review

Schattauer GmbH

Hermansky-Pudlak syndrome

Overview of clinical and molecular features and case report of a new HPS-1 variantHermansky-Pudlak-SyndromÜberblick über klinische und molekulare Eigenschaften und Fallbericht einer neuen HPS-1-Variante

I. Sánchez-Guiu

¹Centro Regional de Hemodonación, Hospital Morales Meseguer, University of Murcia, IMIB, Spain

,

J. M. Torregrosa

¹Centro Regional de Hemodonación, Hospital Morales Meseguer, University of Murcia, IMIB, Spain

,

F. Velasco

²Servicio de Hematología, HU Reina Sofía de Córdoba, University of Córdoba, Spain

,

A. I. Antón

¹Centro Regional de Hemodonación, Hospital Morales Meseguer, University of Murcia, IMIB, Spain

,

M. L. Lozano

¹Centro Regional de Hemodonación, Hospital Morales Meseguer, University of Murcia, IMIB, Spain

,

V. Vicente

¹Centro Regional de Hemodonación, Hospital Morales Meseguer, University of Murcia, IMIB, Spain

,

J. Rivera

¹Centro Regional de Hemodonación, Hospital Morales Meseguer, University of Murcia, IMIB, Spain

› Institutsangaben

Summary

Hermansky-Pudlak syndrome (HPS) is a rare, autosomal recessive disorder affecting lysosome-related organelles (LRO), including dense platelet granules. HPS causes oculo- cutaneous hypopigmentation, bleeding diathesis and granulomatous colitis or pulmonary fibrosis. To date, there is no curative treatment and the clinical management depends on the severity of symptoms. A prompt diagnosis of HPS patients could improve their quality of life and clinical management. However, the absence of a specific platelet function test, the wide molecular heterogeneity, and the lack of phenotypegenotype correlations hamper the rapid diagnosis. Nine subtypes of HPS have been identified as a result of mutations in nine genes that codify for proteins involved in formation and shuttle of the LRO. The molecular characterization of patients and knowledge derived from animal models of HPS contribute to the understanding of biogenesis and function of the LRO.

This paper describes a patient with a novel homozygous nonsense mutation causing HPS and provides a review of the literature focusing on recent advances in the molecular characterization and physiopathology of HPS.

Zusammenfassung

Das Hermansky-Pudlak-Syndrom (HPS) ist eine seltene, autosomal-rezessive Krankheit, die Lysosom-relevante Organellen (LRO) und insbesondere elektronendichte Granula beeinträchtigt. HPS verursacht okulokutane Hypo -pigmentierung, hämorrhagische Diathese und granulomatöse Kolitis sowie Lungen -fibrose. Zurzeit existiert keine kurative Therapie, die klinische Behandlung hängt vom Schweregrad der Symptome ab. Eine frühzeitige Diagnose von HPS-Patienten könnte die Lebensqualität und klinische Behandlung verbessern. Das Fehlen eines spezifischen Thrombozytenfunktionstests, die breite molekulare Heterogenität und die fehlende Phäno typ-Genotyp-Korrelation erschweren jedoch eine schnelle Diagnostik. Neun HPS-Subtypen wurden als Folge von Mutationen in neun Genen identifiziert, die Proteine kodieren, welche bei der Bildung und Ausscheidung der LRO beteiligt sind. Die molekulare Charakterisierung von Patienten und das aus HPS-Tiermodellen erlangte Wissen tragen zum weiteren Verständnis der Biogenese und Funktion der LRO bei.

Diese Arbeit beschreibt einen Patienten mit neuartiger homozygoter, HPS-verursachender Nonsense-Mutation und bietet einen Literaturüberblick mit Schwerpunkt auf jüngste Fortschritte in der molekularen Charakterisierung und Pathophysiologie des HPS.

Keywords

Keywords

Hermansky-Pudlak syndrome - inherited platelet disorders - dense granules

Schlüsselwörter

Schlüsselwörter

Hermansky-Pudlak-Syndrom - erbliche Blut -gerinnungsstörung - dichte Granula

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