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Diagnostik der primären ziliären Dyskinesie

Diagnostics of primary ciliary dyskinesia

  • Leitthema
  • Published:
Der Pneumologe Aims and scope

Zusammenfassung

Die primäre ziliäre Dyskinesie (PCD) ist eine klinisch und genetisch heterogene hereditäre Erkrankung. Der Phänotyp der Erkrankung erklärt sich durch angeborene Defekte respiratorischer Flimmerhärchen (Zilien). Aufgrund einer verminderten mukoziliären Reinigung der Atemwege kommt es zu rezidivierenden Infektionen der oberen und unteren Atemwege. Die Hälfte der PCD-Patienten weist aufgrund einer zufälligen Anordnung der Links/Rechts-Körperasymmetrie einen Situs inversus (Kartagener Syndrom) auf. Bei klinischem Verdacht kann die Diagnose durch Elektronenmikroskopie, hochauflösende Immunfluoreszenzmikroskopie und/oder direktmikroskopische Evaluation des Zilienschlages bestätigt werden. Kürzlich konnten Mutationen bei rezessiv vererbter PCD mit äußeren Dyneinarmdefekten in den Genen DNAI1, DNAH5, DNAH11, TXNDC3 nachgewiesen werden. Hierbei finden sich DNAH5-Mutationen in mehr als 50% der Fälle. Selten finden sich Mutationen bei Jungen mit X-chromosomal rezessiver PCD, assoziiert mit Retinitis pigmentosa (RPGR) oder einem komplexen mentalen Retardierungssyndrom mit Makrozephalie (OFD1).

Abstract

Primary ciliary dyskinesia (PCD) is a phenotypically and genetically heterogeneous genetic disorder. The respiratory disease phenotype which is characterized by upper and lower airway infections results from inborn defects of respiratory cilia responsible for defective mucociliary clearance. Randomization of left/right body asymmetry is responsible for situs inversus (Kartagener’s syndrome) in half of affected individuals. As a screening test nasal nitric oxide measurement can be used. Establishment of the diagnosis currently relies on electron microscopy, high-resolution immunofluorescence analysis, and/or direct evaluation of ciliary beat by light microscopy. Recently mutations in the four genes DNAI1, DNAH5, TXNDC3, and DNAH11 that all encode for outer dynein arm proteins have been linked to recessive PCD. For diagnostic testing especially DNAH5 and DNAI1 mutation screening is useful, because they are responsible for more than 50% of PCD cases with outer dynein arm defects. Rarely mutations in RPGR (PCD + retinitis pigmentosa) and OFD1 (PCD + complex mental retardation syndrome) have been identified in X-linked recessive PCD variants.

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Danksagung

Für die langjährige Unterstützung des Forschungsprojektes gilt den Betroffenen und der Selbsthilfegruppe für „Primäre Ciliäre Dyskinesie und Kartagener Syndrom e.V.“ wie auch allen zusendenden Pädiatern, pädiatrischen Pulmologen und Pulmologen ein herzlicher Dank. Der Deutschen Forschungsgemeinschaft und der Michael Wagner-Stiftung „Kinderlachen“ gilt besonderer Dank für die Förderung des Projektes. Besonderer Dank gilt Herrn N. Loges für die Hilfe bei der Bildbearbeitung.

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  1. Zentrum für Kinderheilkunde und Jugendmedizin, Universität Freiburg, Mathildenstraße 1, 79106, Freiburg, Deutschland

    H. Omran

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Omran, H. Diagnostik der primären ziliären Dyskinesie. Pneumologe 4, 267–275 (2007). https://doi.org/10.1007/s10405-007-0152-1

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  • DOI: https://doi.org/10.1007/s10405-007-0152-1

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