Genetic causes of bronchiectasis: primary ciliary dyskinesia.

Published

Journal Article (Review)

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder reflecting abnormalities in the structure and function of motile cilia and flagella, causing impairment of mucociliary clearance, left-right body asymmetry, and sperm motility. Clinical manifestations include respiratory distress in term neonates, recurrent otosinopulmonary infections, bronchiectasis, situs inversus and/or heterotaxy, and male infertility. Genetic discoveries are emerging from family-based linkage studies and from testing candidate genes. Mutations in 2 genes, DNAI1 and DNAH5, frequently cause PCD as an autosomal recessive disorder. A clinical genetic test has been recently established for DNAI1 and DNAH5, which involves sequencing 9 exons that harbor the most common mutations. This approach will identify at least one mutation in these 2 genes in approximately 25% of PCD patients. If biallelic mutations are identified, the test is diagnostic. If only one mutation is identified, the full gene may be sequenced to search for a trans-allelic mutation. As more disease-causing gene mutations are identified, broader genetic screening panels will further identify patients with PCD. Ongoing investigations are beginning to identify genetic mutations in novel clinical phenotypes for PCD, such as congenital heart disease and male infertility, and new associations are being established between 'ciliary' genetic mutations and clinical phenotypes.

Full Text

Duke Authors

Cited Authors

  • Morillas, HN; Zariwala, M; Knowles, MR

Published Date

  • 2007

Published In

Volume / Issue

  • 74 / 3

Start / End Page

  • 252 - 263

PubMed ID

  • 17534128

Pubmed Central ID

  • 17534128

International Standard Serial Number (ISSN)

  • 0025-7931

Digital Object Identifier (DOI)

  • 10.1159/000101783

Language

  • eng

Conference Location

  • Switzerland