Monatsschrift Kinderheilkunde

, Volume 153, Issue 3, pp 246–254 | Cite as

Genetische Defekte bei primärer ziliärer Dyskinesie

Leitthema: Chronische Bronchitis
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Zusammenfassung

Die primäre ziliäre Dyskinesie (PCD) ist genetisch und klinisch heterogen. Sie wird in der Regel autosomal-rezessiv vererbt. Selten sind eine dominante oder X-chromosomal-rezessive Vererbung. Bei Betroffenen führt eine Dysmotilität der Flimmerhärchen (Zilien) zu einer verminderten mukoziliären Reinigung der Atemwege. Dies bedingt das Auftreten chronischer Entzündungen der Atemwege und von Bronchiektasen. Mittels Elektronenmikroskopie können häufig ultrastrukturelle Defekte der inneren oder äußeren Dyneinarme, welche die Zilienbewegung vermitteln, nachgewiesen werden. Rezessive Mutationen der für Dyneinproteine des äußeren Dyneinarms kodierenden Gene DNAI1 (9p13–p21) undDNAH5 (5p15–p14) verursachen PCD und die Randomisierung der Links-rechts-Körperasymmetrie (Situs inversus). Erkrankte weisen ultrastrukturelle Defekte des äußeren Dyneinarms auf. Selten führen Mutationen desRPGR-Gens zu einer X-chromosomal-rezessiv vererbten PCD-Variante. Diese Patienten sind obligat männlich und weisen eine Retinitis pigmentosa und teilweise eine Innenohrschwerhörigkeit auf. Mehrere weitere Genorte konnten für PCD identifiziert werden. Eine molekulargenetische Diagnostik ist aufwändig, führt aber in 10–20% der Fälle zu einem Mutationsnachweis.

Schlüsselwörter

Primäre ziliäre Dyskinesie (PCD)  Dysmotilität der Flimmerhärchen Zilien Dyneinproteine Molekulargenetische Diagnostik 

Genetische Defekte bei primärer ziliärer Dyskinesie

Abstract

Primary ciliary dyskinesia (PCD) is a clinically and genetically heterogeneous disorder that is usually inherited as an autosomal recessive disease trait. Very occasionally cases of dominant or X-chromosomal recessive transmission are observed. Dyskinetic cilia cause reduced mucociliary clearance of the airways, resulting in chronic inflammatory processes of the upper and lower respiratory system, often with the development of bronchiectasia. Electron microscopy frequently reveals ultrastructural defects of the inner (IDA) or outer dynein arms (ODA), which are responsible for ciliary bending. Recessive mutations of the DNAI1 (9p13-p21) and DNAH5 (5p15-p14) genes, i.e. those encoding ODA dynein proteins, cause PCD and randomization of left/right body asymmetry. Ultrastructural ODA defects are a constant finding in PCD. In rare instances, mutations of the RPGR gene are responsible for an X-chromosomal recessive PCD variant. Those affected are male: all these patients also suffer from retinitis pigmentosa, and some of them have sensory hearing deficits in addition. Several other gene loci for PCD (19q13.3-qter) have been recognized. Molecular genetic testing in PCD is laborious, but identifies the underlying genetic defect in ~10–20% of cases.

Keywords

Primary ciliary dyskinesia (PCD) Dyskinesia of cilia Cilia Dynein proteins Molecular genetic diagnostic testing 

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Copyright information

© Springer Medizin Verlag 2005

Authors and Affiliations

  1. 1.Zentrum für Kinderheilkunde und JugendmedizinUniversität Freiburg
  2. 2.Zentrum für Kinderheilkunde und JugendmedizinUniversität FreiburgFreiburg

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